From 1db702baee76bd3730c04ca5b2af85d647da20b8 Mon Sep 17 00:00:00 2001
From: Li Shumin <smli@bal13.cs.hku.hk>
Date: Sun, 20 Oct 2024 18:25:28 +0800
Subject: [PATCH] upload PM3-bench

---
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 PM3-Bench/README.md           |  24 ++++++++++++++++++++++++
 README.md                     |   5 ++++-
 images/PM3-bench.png          | Bin 0 -> 219759 bytes
 4 files changed, 29 insertions(+), 1 deletion(-)
 create mode 100644 PM3-Bench/PM3_Bench_data.json
 create mode 100644 images/PM3-bench.png

diff --git a/PM3-Bench/PM3_Bench_data.json b/PM3-Bench/PM3_Bench_data.json
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+[{"CinGen ID":"CA114363","Variant Name":"NM_000277.1:c.965C>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":1301200,"Raw Comment":"Two missense mutations causing mild HPA associated with haplotype 12\n88 swedish families. 93 children picked up by NBS\nA322G \/ R408Q \u00e2\u0080\u0093300uM\/L\nA322G \/ R408W \u00e2\u0080\u0093 250uM\/L\nA322G \/ R408W \u00e2\u0080\u0093 360uM\/L\nA322G \/ R252W \u00e2\u0080\u0093 250uM\/L","Number of Patients":93,"In trans Variants":["p.R408W c.(1222C>T)","p.R408Q c.(1223G>A)","p.R252W c.(754C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA251544","Variant Name":"NM_000277.2:c.194T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":1301201,"Raw Comment":"We amplified and sequenced exon 3 from a PKU proband harboring the R408W allele on the other chromosome (see John et al., 1990, family #6). We identified a T to C transition in codon 65 (Fig. 1A). This substitution changes an isoleucine codon (ATT) to one for threonine (ACT); no other changes were found in the entire coding region or in the exon intron boundaries of the PAH gene. The I65T mutation, segregated with this haplotype in the nuclear family (Fig. 1B).","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA10585201","Variant Name":"NM_000527.5:c.932A>G","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":1301940,"Raw Comment":"Variant meets PM2 and is identified in an index case with homozygous FH phenotype (plasma cholesterol > 600mg\/dL) and LDLR variant NM_000527.5(LDLR):c.910G>T (p.Asp304Tyr) (ClinVar ID: 251517), classified as Likely pathogenic by these guidelines, in trans (PMID: 1301940), so PM3 is Met.","Number of Patients":1,"In trans Variants":["c.910G>T p.Asp304Tyr"],"labels":"fine-tune"},{"CinGen ID":"CA273936","Variant Name":"NM_000277.2:c.168_168+1delGGinsAA","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":1301942,"Raw Comment":"Patients 1 through 5 were all identified as homozygous for this variant.","Number of Patients":5,"In trans Variants":["homozygous c.168_168+1delGGinsAA "],"labels":"fine-tune"},{"CinGen ID":"CA229532","Variant Name":"NM_000277.2:c.3G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":1301947,"Raw Comment":"The compound heterozygote genotype (IVS-12\/M1I). He had inherited the IVS-12 mutation from his mother, and the haplotype 7 (hpt7) chromosome from his father.","Number of Patients":1,"In trans Variants":["c.IVS-12"],"labels":"fine-tune"},{"CinGen ID":"CA229404","Variant Name":"NM_000277.1:c.1223G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":1312992,"Raw Comment":"In trans with R408W--(ClinGen, P). One patient homozygous for the mutation was found.","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA114364","Variant Name":"NM_000277.1:c.1243G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":1358789,"Raw Comment":"D415N was found in trans with R408W (VarID 577, Pathogenic) in 1 HPA patient.","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229718","Variant Name":"NM_000277.1:c.724C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":1363786,"Raw Comment":"Patient B21-3 genotype L242F\/R252W (VarID 584, Pathogenic\/LP)","Number of Patients":1,"In trans Variants":["p.R252W c.(754C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229705","Variant Name":"NM_000277.2:c.712A>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":1363786,"Raw Comment":"Patient D10-3: T238P\/R408W (VarID 577, Pathogenic)","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229339","Variant Name":"NM_000277.2:c.1092_1106del","Condition":"phenylketonuria","Criterion":"PM3","PMID":1363837,"Raw Comment":"Digestion of genomic DNA using restriction enzyme Hindlll produced an abnormal pattern of hybridization consisting of a 7.5 kb abnormal band with the reduction in the intensity of a 5.0 kb invariant fragment in both the proband and his mother\n(Figure 1). the other mutant allele bore the R408W mutation.","Number of Patients":2,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229721","Variant Name":"NM_000277.2:c.731C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":1363838,"Raw Comment":"This patient had mutant haplotypes 12\/9 and carried the previously described mutation I65T (VarID 636, P\/LP in ClinVar) on the haplotype 9 allele. P244L was on haplotype 12, paternally inherited.","Number of Patients":1,"In trans Variants":["[p.I65T c.(194T>C)]"],"labels":"fine-tune"},{"CinGen ID":"CA229704","Variant Name":"NM_000277.3:c.707-2A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":1563085,"Raw Comment":"This variant was detected in trans with the pathogenic PAH variant p.Arg408Trp (1pt). PMID: 1563085","Number of Patients":1,"In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA251523","Variant Name":"NM_000277.1:c.1222C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":1609797,"Raw Comment":"M1V mutation (VarID 586, P\/LP) was found on four chromosomes, one of the compound heterozygotes also carried the R408W mutation (fig.1, patient P3).","Number of Patients":1,"In trans Variants":["p.M1V c.(1A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229677","Variant Name":"NM_000277.2:c.662A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":1679030,"Raw Comment":"Glu221Gly found in trans with Leu48Ser in a Turkish patient with PKU. L48S is classified as Pathogenic in ClinVar (VarID 608).","Number of Patients":1,"In trans Variants":["p.Leu48Ser c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA2499306877","Variant Name":"NM_000419.5:c.188+471_892-70delinsGCCACCCACAGTGCAATCCCACA","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":1702098,"Raw Comment":"Patient K.W. of PMID: 1702098 is homozygous for this variant (PM2_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.188+471_892-70delinsGCCACCCACAGTGCAATCCCACA "],"labels":"fine-tune"},{"CinGen ID":"CA380144505","Variant Name":"NM_000536.4:c.130G>T","Condition":"recombinase activating gene 2 deficiency","Criterion":"PM3-Supporting","PMID":1728908,"Raw Comment":"Patient P2 from Alizadeh et all (pre-print, not peer reviewed DOI: https:\/\/doi.org\/10.21203\/rs.3.rs-1728908\/v1 ) is homozygous and parents are heterozygous. We can either count this homozygous patient as 0.25p if we consider this variant VUS (which is not enough points to apply PM3 at all) or we can count as 0.5p if we consider this variant to be at least LP (0.5p is enough to apply PM3 at supporting level). I think this variant would be at LEAST LP even without this patient because p.Gly44* is a rare truncating variant in a LOF gene and the ClinGen SCID VCEP has classified at least one downstream truncating variant as LP already (c.829dup p.Tyr277fs)...so it would make no sense that this upstream p.Gly44* variant would be a VUS when it disrupts even more of the protein than a downstream truncation we've already classified as LP. Therefore, I'm considering this as homozygous occurrence, confirmed in trans, LP\/P variant worth 0.5p for PM3. PM3_Supporting is met.","Number of Patients":1,"In trans Variants":["homozygous c.130G>T p.(Gly44*)"],"labels":"fine-tune"},{"CinGen ID":"CA251523","Variant Name":"NM_000277.1:c.1222C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":1971147,"Raw Comment":"One French-Canadian proband of consanguineous parents (family 3; fig. 1) is homozygous for the R408W mutation on haplotype 1.","Number of Patients":1,"In trans Variants":["homozygous c.1222C>T p.(Arg408Trp)"],"labels":"fine-tune"},{"CinGen ID":"CA229337","Variant Name":"NM_000277.2:c.1092_1094del","Condition":"phenylketonuria","Criterion":"PM3","PMID":1975559,"Raw Comment":"The c.1092_1094delTCT variant in PAH has been previously reported as a single variant, found in trans with the Pathogenic variant (per internal PAH ClinGen Working Group classification, see ClinVar allele ID 15635) p.Gly272Ter in one proband with classic PKU (PMID: 1975559); phase was confirmed via parental testing (PM3).","Number of Patients":1,"In trans Variants":["p.Gly272Ter c.(814G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA115285","Variant Name":"NM_000022.4:c.631C>T","Condition":"adenosine deaminase deficiency","Criterion":"PM3","PMID":2166947,"Raw Comment":"Patient was found heterozygous for R211C & L107P which is classified as likely pathogenic by SCID VCEP (1 pt.) (PM3) (PMID: 2166947)","Number of Patients":1,"In trans Variants":["p.R211C c.(631C>T)","p.L107P c.(320T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA123226","Variant Name":"NM_000212.2:c.433G>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":2428841,"Raw Comment":"1 patient with variant GT was homozygous for Asp145Tyr","Number of Patients":1,"In trans Variants":["homozygous c.433G>T p.(Asp145Tyr)"],"labels":"fine-tune"},{"CinGen ID":"CA114360","Variant Name":"NM_000277.2:c.1A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":2574002,"Raw Comment":"A proband was homozygous for this mutation (A-to-G transition (met-val) in codon1]. In other probands, the codon1 mutation was inherited once with the splice junction mutation in exon 12 (c.1315+1G>A),and was inherited twice with a mutation on haplotype 1.","Number of Patients":"2","In trans Variants":["homozygous c.1A>G p.?","c.1315+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA402998134","Variant Name":"NM_138924.3:c.115A>G","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":3730571,"Raw Comment":"The c.115A>G(p.Lys39Glu) variant was identified in a proband alongside the pathogenic variant c.328-2A>G (PMID:3730571). Phase analysis was unclear, meeting the Cerebral Creatine Deficiency Syndromes metric for PM3_Supporting. ","Number of Patients":1,"In trans Variants":["c.328-2A>G"],"labels":"fine-tune"},{"CinGen ID":"CA913184731","Variant Name":"NM_000419.5:c.2473_2478delinsTCACCAGGGCCTTCACCTCAGCATCCACCAG","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":7529063,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia (PMID: 7529063). This individual was homozygous for the variant (0.5 PM3 points, PM3_Supporting). ","Number of Patients":1,"In trans Variants":["homozygous c.2473_2478delinsTCACCAGGGCCTTCACCTCAGCATCCACCAG p.(Val825Serfs*106)"],"labels":"fine-tune"},{"CinGen ID":"CA115839","Variant Name":"NM_000419.4:c.1073G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":7706461,"Raw Comment":"Patient KJ is homozygous for Arg358His (reported as Arg327His) as a result of consanguinity.","Number of Patients":1,"In trans Variants":["homozygous c.1073G>A p.(Arg358His)"],"labels":"fine-tune"},{"CinGen ID":"CA229884","Variant Name":"NM_000277.3:c.970-6T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":7766957,"Raw Comment":"PMID: 7766957 reports Patient B compound heterozygous for c.970-6T>G and R413P (ClinVar592 Pathogenic), with trans phasing confirmed through cloning.","Number of Patients":1,"In trans Variants":["p.R413P c.(1238G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229599","Variant Name":"NM_000277.2:c.512G>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":7833954,"Raw Comment":"Patient genotype: G171A \/ IVSl0nt546. parental DNA not available.","Number of Patients":1,"In trans Variants":["IVSl0nt546"],"labels":"fine-tune"},{"CinGen ID":"CA229743","Variant Name":"NM_000277.1:c.755G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":7833954,"Raw Comment":"In Table 1, in trans with p.Pro407fs","Number of Patients":1,"In trans Variants":["p.Pro407fs"],"labels":"fine-tune"},{"CinGen ID":"CA229269","Variant Name":"NM_000277.2:c.1012G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":7913581,"Raw Comment":"Seen in 1 PKU patient. The mother of the proband carries the D338Y mutation; the paternal mutation is F299C (VarID 613, Pathogenic\/LP in ClinVar).","Number of Patients":1,"In trans Variants":["p.F299C c.(896T>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229633","Variant Name":"NM_000277.2:c.581T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":7981714,"Raw Comment":"Patient F: V245A (VarID632, Path) \/L194P. The mutations identified were confirmed by restriction analysis of PCR products reamplified from genomic DNA in affected subjects and their parents.","Number of Patients":1,"In trans Variants":["p.V245A c.(734T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA114369","Variant Name":"NM_000277.1:c.1139C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":7981714,"Raw Comment":"In all patients carrying T380M, mutations known to cause classic PKU (R408W, R261Q, I65T, and F299C) were identified on the other chromosome. The mutations identified were confirmed by restriction analysis of PCR products reamplified from genomic DNA in affected subjects and their parents.","Number of Patients":"NA","In trans Variants":["p.F299C c.(896T>G)","p.R408W c.(1222C>T)","p.R261Q c.(782G>A)","p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA114372","Variant Name":"NM_000277.2:c.734T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":7981714,"Raw Comment":"Patient F: V245A\/L194P (VarID 102742, P\/LP)","Number of Patients":1,"In trans Variants":["p.L194P c.(581T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA114372","Variant Name":"NM_000277.2:c.734T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":8088845,"Raw Comment":"Patient K Genotype: V245A\/IVS-12nt1. Patient L: V245A\/R408W. Patient M: V245A\/Y414C","Number of Patients":3,"In trans Variants":["IVS-12nt1","p.R408W c.(1222C>T)","p.Y414C c.(1241A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA212751","Variant Name":"NM_000277.2:c.1065+3A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":8088845,"Raw Comment":"2 siblings compound heterozygous for Y414C (Pathogenic in ClinVar)","Number of Patients":2,"In trans Variants":["p.Y414C c.(1241A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA114367","Variant Name":"NM_000277.1:c.1169A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":8088845,"Raw Comment":"Found in Patient V: E390G\/IVS-12nt1 (VarID 576) pathogenic in ClinVar","Number of Patients":1,"In trans Variants":["IVS-12nt1"],"labels":"fine-tune"},{"CinGen ID":"CA229401","Variant Name":"NM_000277.3:c.121C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":8268925,"Raw Comment":"L41F seen in trans with R261Q (VarID 582, Pathogenic\/LP in ClinVar) in 1 patient with mild PKU.","Number of Patients":1,"In trans Variants":["p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA115837","Variant Name":"NM_000419.5:c.818G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":8282784,"Raw Comment":"The patient from PMID: 8282784 is homozygous for Gly273Asp.","Number of Patients":1,"In trans Variants":["homozygous c.818G>A p.(Gly273Asp)"],"labels":"fine-tune"},{"CinGen ID":"CA915940805","Variant Name":"NM_000212.3:c.161_165+1delinsCTGATT","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":8471765,"Raw Comment":"This variant has been detected homozygous in one GT proband (05pt; PM3_supporting; PMID: 8471765)","Number of Patients":1,"In trans Variants":["homozygous c.161_165+1delinsCTGATT "],"labels":"fine-tune"},{"CinGen ID":"CA229839","Variant Name":"NM_000277.1:c.899C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":8533759,"Raw Comment":"A300V found in trans with R408W (VarID 577) Pathogenic In ClinVar. The exact inheritance of mutations and STR alleles was determined in each family.","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229574","Variant Name":"NM_000277.2:c.47_48delCT","Condition":"phenylketonuria","Criterion":"PM3","PMID":8535445,"Raw Comment":"47delCT found in trans with L48S in Family 10.","Number of Patients":1,"In trans Variants":["p.L48S c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229551","Variant Name":"NM_000277.3:c.442G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":8535445,"Raw Comment":"The variant c.442G>A (p.Gly148Ser) was document with the pathogenic variant c.194T>C (p.Ile65Thr)(ClinVar ID: 636) in a family with a phenotype of moderate + normal retardation, and with the pathogenic variant c.473G>A (p.Arg158Gln)(ClinVar ID: 587) in a family with a moderate retardation phenotype. The families belong to a study of 4 families with untreated PKU in Australia.(PMID: 8535445).","Number of Patients":2,"In trans Variants":["p.Arg158Gln c.(473G>A)","p.Ile65Thr c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229481","Variant Name":"NM_000277.2:c.199T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":8592329,"Raw Comment":"Patient III-4 genotype: L48S (maternal)\/S67P (paternal). L48S: VarID608, Pathogenic.","Number of Patients":1,"In trans Variants":["p.L48S c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA273109","Variant Name":"NM_000277.1:c.638T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":8632937,"Raw Comment":"PAH Genotype: L213P\/R261X (VarID 610, Pathogenic)","Number of Patients":1,"In trans Variants":["p.R261X"],"labels":"fine-tune"},{"CinGen ID":"CA229539","Variant Name":"NM_000277.2:c.434A>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":8659548,"Raw Comment":"Patient I\/1140\/LMA-10: Allele1: D145V, Allele 2: V388M (Pathogenic in ClinVar).","Number of Patients":1,"In trans Variants":["p.V388M c.(1162G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229724","Variant Name":"NM_000277.2:c.733G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":8659548,"Raw Comment":"V245L seen with N133Ql34fsdel4bp ((398-401)del4bp)","Number of Patients":"NA","In trans Variants":["N133Ql34fsdel4bp"],"labels":"fine-tune"},{"CinGen ID":"CA229610","Variant Name":"NM_000277.3:c.529G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":8659548,"Raw Comment":"Allele 2: F39L Parental testing not reported.","Number of Patients":"NA","In trans Variants":["p.F39L c.(115T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229845","Variant Name":"NM_000277.2:c.912G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":8659548,"Raw Comment":"Table 4, Patient I\/1059\/ITDE-20, Genotype Q304Q\/K363fsdelG. Parental testing not reported.","Number of Patients":1,"In trans Variants":["K363fsdelG"],"labels":"fine-tune"},{"CinGen ID":"CA229350","Variant Name":"NM_000277.1:c.1114A>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":8807319,"Raw Comment":"Proband 33: A300S (VarID92751, Pathogenic)\/T372S","Number of Patients":1,"In trans Variants":["p.A300S c.(898G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229673","Variant Name":"NM_000277.1:c.649T>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":8807319,"Raw Comment":"C217G in trans with P281L in PKU patient. P281L is classified as pathogenic ClinVar (VarID 589)","Number of Patients":1,"In trans Variants":["p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229836","Variant Name":"NM_000277.2:c.889C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":8807331,"Raw Comment":"Detected in trans with a splicing mutation in a patient with classic PKU (table 2). Serum phenylalanine 472 micromolar.","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229378","Variant Name":"NM_000277.3:c.1196_1199del","Condition":"phenylketonuria","Criterion":"PM3","PMID":8807331,"Raw Comment":"Case 154 (PMID: 8807331) is compound heterozygous for c.196_1199del and Arg408Trp (ClinVar 577, classified Pathogenic by the PAH VCEP; PM3).","Number of Patients":1,"In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA273936","Variant Name":"NM_000277.2:c.168_168+1delGGinsAA","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":8825928,"Raw Comment":"Patient LGL5044 was identified as compound heterozygous for this variant and Arg408Trp (ClinVar 577, Pathogenic).","Number of Patients":1,"In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229439","Variant Name":"NM_000277.3:c.136G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":8829656,"Raw Comment":"The variant c.136G>A (p.Gly46Ser) was documented in trans with seven other PAH pathogenic or likely pathogenic variants in 15 Norwegian patients with mild and classic PKU. Haplotype analysis of index cases and parents was conducted, when necessary siblings were also investigated (PMID: 8829656). PM3_Very Strong (14 points).","Number of Patients":15,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229341","Variant Name":"NM_000277.1:c.1097C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":8830172,"Raw Comment":"Patient F50: R158Q (VarID 587, Pathogenic) \/P366H, pre-treatment Phe level 720 umol\/L","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229372","Variant Name":"NM_000277.1:c.1181A>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":8830172,"Raw Comment":"Family F32, genotype R261Q\/D394A. R261Q (VarID 582, Pathogenic\/LP in ClinVar)","Number of Patients":1,"In trans Variants":["p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA032391","Variant Name":"NM_000527.5:c.1176C>A","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":8831933,"Raw Comment":"variant meets PM2 and was identified in 1 index case who also carries NM_000527.5(LDLR):c.1A>T (p.Met1Leu), confirmed in trans, who has LDL 17.3mmol\/L from PMID: 8831933 (Langenhoven et al. 1996 Aug 23;125(1):111-9. \n--- 2nd variant is classified as Pathogenic with these guidelines, so PM3 is met","Number of Patients":1,"In trans Variants":["[c.1A>T p.Met1Leu]"],"labels":"fine-tune"},{"CinGen ID":"CA115839","Variant Name":"NM_000419.4:c.1073G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":8883261,"Raw Comment":"The proband is homozygous for Arg358His. 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.1073G>A p.(Arg358His)"],"labels":"fine-tune"},{"CinGen ID":"CA229371","Variant Name":"NM_000277.1:c.1180G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":8889590,"Raw Comment":"Patient with classical PKU has D394H with IVS10nt-11g>a (VarID 607, Pathogenic in ClinVar) on the second chromosome.","Number of Patients":1,"In trans Variants":["IVS10nt-11g>a"],"labels":"fine-tune"},{"CinGen ID":"CA229456","Variant Name":"NM_000277.2:c.168+6T>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":8889590,"Raw Comment":"One patient was described as compound heterozygous for the c.168+6T>G and c.47_48delCT (ClinVar 102696, Pathogenic) variants. Parental confirmation not reported.","Number of Patients":1,"In trans Variants":["c.47_48delCT p.(Ser16*)"],"labels":"fine-tune"},{"CinGen ID":"CA251538","Variant Name":"NM_000277.1:c.1066-11G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":8990013,"Raw Comment":"11 Gypsy PKU patients were screened for the presence of IVS10nt546. 8 were homozygous and 3 heterozygous. R252W was found in two heterozygous siblings. (VarID 584, P\/LP). The results were confirmed in the parents. 23 non-Gypsy unrelated PKU patientsl carry mutation IVS10nt546: 8 homozygotes and 15 compound heterozygous.","Number of Patients":24,"In trans Variants":["homozygous c.1066-11G>A ","p.R252W c.(754C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA042622","Variant Name":"NM_000527.5:c.269A>G","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":9026534,"Raw Comment":"variant meets PM2 and was identified in\n- 1 index case with phenotype of homozygous FH (cholesterol of 20.7mmol\/L) and also NM_000527.5(LDLR):c.912C>G (p.Asp304Glu), Likely pathogenic by these guidelines, from PMID 9026534 (Webb et al., 1996), UK\nso PM3 is met","Number of Patients":1,"In trans Variants":["c.912C>G p.Asp304Glu"],"labels":"fine-tune"},{"CinGen ID":"CA172240","Variant Name":"NM_004004.5:c.71G>A","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":9139825,"Raw Comment":"Family segregating with homozygous W24* variant in four individuals with hearing loss.","Number of Patients":4,"In trans Variants":["homozygous c.71G>A p.(Trp24*)"],"labels":"fine-tune"},{"CinGen ID":"CA229348","Variant Name":"NM_000277.3:c.1112A>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":9169088,"Raw Comment":"Reported with IVS10-11G>A, parental analysis not reported PMID: 9169088 (0.5)","Number of Patients":"NA","In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA500260678","Variant Name":"NM_000419.5:c.3092_3093dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":9215749,"Raw Comment":"This variant is found in trans (phase not confirmed) with the c.3060+2T>C variant (PMID: 9215749), classified as Pathogenic by the ClinGen Platelet Disorders VCEP. Therefore, 0.5 points is applied here for a pathogenic variant not confirmed in trans.","Number of Patients":"1","In trans Variants":["c.3060+2T>C"],"labels":"fine-tune"},{"CinGen ID":"CA915940648","Variant Name":"NM_000212.3:c.1053_1058del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":9226167,"Raw Comment":"This variant has been detected in at least 4 probands with Glanzmann thrombasthenia (3 patients from PMID: 9226167, 1 patient from internal PD VCEP data). These individuals were all homozygous for the variant (1 point, PM3). \n\n","Number of Patients":3,"In trans Variants":["homozygous c.1053_1058del p.(Ile351_Gly353delinsMet)"],"labels":"fine-tune"},{"CinGen ID":"CA172217","Variant Name":"NM_004004.5:c.167del","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":9285800,"Raw Comment":"1 allele from chr 13 linked NSRD patient, variant result in loss of restriction site, interpreted as likely disease causing, 1 cpd het with 35delG and this variant,","Number of Patients":1,"In trans Variants":["c.35delG p.(Gly12Valfs*2)"],"labels":"fine-tune"},{"CinGen ID":"CA114372","Variant Name":"NM_000277.2:c.734T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":9298832,"Raw Comment":"V245A seen in 2 patients. Once with R252W (varID 584, P\/LP). Once with R408W (VarID 577, Pathogenic)","Number of Patients":2,"In trans Variants":["p.R408W c.(1222C>T)","p.R252W c.(754C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA220590","Variant Name":"NM_000277.2:c.890G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9298832,"Raw Comment":"Detected in trans with pathogenic p.R408W (ClinVar: 577) in 4 patients. Table 1\nAlso IVS2 (c.168+5G>A; VARID 102606, LP); R252W (VarID 584, P). Parental analysis not performed.","Number of Patients":4,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229419","Variant Name":"NM_000277.2:c.125A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":9380432,"Raw Comment":"K42I, a novel mutation, and expressed in vivo with E280K (a so-called \u00e2\u0080\u009csevere\u00e2\u0080\u009d allele) confers a 6% oxidation value, implying that K42I is \u00e2\u0080\u009cmild\u00e2\u0080\u009d(Table 4).","Number of Patients":0,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA180669","Variant Name":"NM_000260.4:c.2476G>A","Condition":"Usher syndrome","Criterion":"PM3","PMID":9382091,"Raw Comment":"28 families with Usher Type 1B were tested for variants in MYO7A. The p.Ala826Thr variant was identified in the homozygous state in 4 Moroccan families (counting those with different haplotypes) and in the compound heterozygous state in a fifth family in trans with the p.Gly214Arg variant. (p.Gly214Arg is classified as pathogenic by 4 clinical labs in ClinVar).","Number of Patients":8,"In trans Variants":["homozygous c.2476G>A p.(Ala826Thr)","p.Gly214Arg c.(640G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA114362","Variant Name":"NM_000277.1:c.1241A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":9399896,"Raw Comment":"compound het and homozygous patients","Number of Patients":"NA","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229453","Variant Name":"NM_000277.2:c.168+5G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9429153,"Raw Comment":"c.168+5G>A has been observed in trans with R297H (ClinVar 92750, Pathogenic).","Number of Patients":1,"In trans Variants":["p.R297H c.(890G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA273106","Variant Name":"NM_000277.1:c.1208C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":9429153,"Raw Comment":"A403V found in 13 Polish patients in trans with 4 different known pathogenic variants. R408W, R158Q, P281L, IVS10.","Number of Patients":13,"In trans Variants":["p.R408W c.(1222C>T)","p.R158Q c.(473G>A)","p.P281L c.(842C>T)","IVS10"],"labels":"fine-tune"},{"CinGen ID":"CA229679","Variant Name":"NM_000277.1:c.665A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9429153,"Raw Comment":"D222G found in trans with A104D (VarID 102650, Pathogenic in ClinVar) in 1 PKU patient.","Number of Patients":1,"In trans Variants":["p.A104D c.(311C>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229515","Variant Name":"NM_000277.2:c.311C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9429153,"Raw Comment":"Patient genotype: A104D\/D222G (VarID 102775, clinical significance not provided). Patient genotype: Y414C (VarID 593, Pathogenic)\/A104D.","Number of Patients":2,"In trans Variants":["p.Y414C c.(1241A>G)","p.D222G c.(665A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA286507","Variant Name":"NM_000277.1:c.722G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9429153,"Raw Comment":"R241H found in 3 patient with mild PKU, in trans with R252W (VarID 584, Pathogenic\/Likely Pathogenic in ClinVar), IVS1O (VarID 607, Pathogenic in ClinVar), R408W (VarID 577, Pathogenic in ClinVar).","Number of Patients":3,"In trans Variants":["IVS1O","p.R408W c.(1222C>T)","p.R252W c.(754C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229272","Variant Name":"NM_000277.3:c.1021A>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":9452062,"Raw Comment":"Patient 429 of PMID: 9452062 is compound heterozygous for K341X and c.1315+1G>A (ClinVar 576, Pathogenic reviewed by PAH expert panel). Confirmation of trans phase was not reported.","Number of Patients":1,"In trans Variants":["c.1315+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229429","Variant Name":"NM_000277.2:c.1315+2T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9452062,"Raw Comment":"Found in trans with F39del in a single patient with classic PKU","Number of Patients":1,"In trans Variants":["F39del"],"labels":"fine-tune"},{"CinGen ID":"CA229775","Variant Name":"NM_000277.1:c.805A>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":9521426,"Raw Comment":"PMID 9521426: c.842+3G>C\/c.805A>C (I269L) in one patient with non-PKU HPA","Number of Patients":1,"In trans Variants":["c.842+3G>C"],"labels":"fine-tune"},{"CinGen ID":"CA229429","Variant Name":"NM_000277.2:c.1315+2T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9521426,"Raw Comment":"Two patients, one in trans with Y414C (mild PKU) and one in trans with R261X (classic PKU","Number of Patients":2,"In trans Variants":["p.R261X","p.Y414C c.(1241A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229643","Variant Name":"NM_000277.1:c.601C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9521426,"Raw Comment":"Patient F99: Genotype H201Y\/IVS10nt546 (VarID:607, Pathogenic); Phenotype non-PKU HPA.","Number of Patients":1,"In trans Variants":["IVS10nt546"],"labels":"fine-tune"},{"CinGen ID":"CA229460","Variant Name":"NM_000277.2:c.169-13T>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9521426,"Raw Comment":"IVS2nt-13 in F84 was maternally inherited. The second mutation was L213P (varID 92747, Pathogenic\/LP).","Number of Patients":1,"In trans Variants":["p.L213P c.(638T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229814","Variant Name":"NM_000277.2:c.842+3G>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9521426,"Raw Comment":"Patient F100: c.842+3g\u00e2\u0086\u0092c (IVS7nt3)\/c.805A\u00e2\u0086\u0092C (I269L) (VarID 102842, Pathogenic).","Number of Patients":1,"In trans Variants":"[\"c.805A>C p.I269L\"]","labels":"fine-tune"},{"CinGen ID":"CA229821","Variant Name":"NM_000277.2:c.848T>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9521426,"Raw Comment":"2 patients, 1 in trans with Y414C and 1 in trans with c.1066-11>G","Number of Patients":2,"In trans Variants":["c.1066-11>G","p.Y414C c.(1241A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229479","Variant Name":"NM_000277.2:c.194T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":9521426,"Raw Comment":"c.194T>A (p.I65N) was identified in trans to the known c.143T>C (L48S) mutation in a patient with classic PKU. Segregation was tested for seven of the eight new mutations by DGGE (DG) and\/or DNA sequencing(DS) and\/or enzymatic digestion (ED). Parental origin of I65N could not be ascertained because the father\u00e2\u0080\u0099s DNA was not available.","Number of Patients":1,"In trans Variants":["c.143T>C p.L48S"],"labels":"fine-tune"},{"CinGen ID":"CA229866","Variant Name":"NM_000277.3:c.941del","Condition":"phenylketonuria","Criterion":"PM3","PMID":9600453,"Raw Comment":"Patient F536 of PMID: 9600453 is compound heterozygous for c.941del and c.1066-11G>A (ClinVar 607, Pathogenic with expert panel review).","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA252228","Variant Name":"NM_007123.5:c.4338_4339delCT","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":9624053,"Raw Comment":"Homozygous c.4353-54delCT is mapped to be equivalent to this variant by HGMD and it was found to be present in a homozygous state in III-1 and III-3 in family #536. There were 2 unaffected individuals as well and the non consanguineous parents were healthy.","Number of Patients":2,"In trans Variants":["homozygous c.4338_4339delCT p.(Cys1447Glnfs*29)"],"labels":"fine-tune"},{"CinGen ID":"CA251523","Variant Name":"NM_000277.1:c.1222C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":9634518,"Raw Comment":"R408W\/IVS12nt1g>a (VarID576, Pathogenic)","Number of Patients":1,"In trans Variants":["IVS12nt1g>a"],"labels":"fine-tune"},{"CinGen ID":"CA915940646","Variant Name":"NM_000419.5:c.575_576insGACAAG","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":9739052,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia (Patient KO from PMID: 9739052). This patient was homozygous for the variant (0.5 PM3 points, PM3_Supporting). \n\n\"Patient KO appeared homozygous for the 6-bp insertion.\" Parents of KO were shown to each be heterozygous for the variant. ","Number of Patients":1,"In trans Variants":["homozygous c.575_576insGACAAG p.(Phe191_Ser192insArgThr)"],"labels":"fine-tune"},{"CinGen ID":"CA626224450","Variant Name":"NM_000419.5:c.3017dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":9798966,"Raw Comment":"Patient DV of PMID: 9798966 is compound heterozygous for paternal c.3017dup and maternal Tyr471Ter (classified Pathogenic by the PD-VCEP) variants.","Number of Patients":1,"In trans Variants":["p.Tyr471Ter c.(1413C>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229414","Variant Name":"NM_000277.1:c.1238G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":9860305,"Raw Comment":"We confirmed that 7 patients were homozygous for R413P by using direct sequencing and demonstrated that the parents were heterozygous carriers for the same mutations as the patients.","Number of Patients":7,"In trans Variants":["homozygous c.1238G>C p.(Arg413Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA251543","Variant Name":"NM_000277.1:c.1162G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":9860305,"Raw Comment":"Compound het with severe mutation, showed 8% activity, and classic pku","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA8602816","Variant Name":"NM_000419.4:c.2113T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":9920835,"Raw Comment":"The proband is a compound heterozygote with the paternally derived c.624+2C>A variant and the maternal c.2113T>C (p.Cys705Arg).","Number of Patients":1,"In trans Variants":["c.624+2C>A"],"labels":"fine-tune"},{"CinGen ID":"CA10584817","Variant Name":"NM_000527.5:c.265T>C","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":9974426,"Raw Comment":"Variant meets PM2 and is identified in an index case with homozygous FH phenotype (LDL = 18.05 mmol\/L) and LDLR variant c.1775G>A\/p.(Gly592Glu), classified as Pathogenic by these guidelines, in trans, from ltaly (PMID: 9974426), so PM3 is Met.","Number of Patients":1,"In trans Variants":"[\"c.1775G>A p.Gly592Glu\"]","labels":"fine-tune"},{"CinGen ID":"CA400032350","Variant Name":"NM_000212.2:c.1702T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":10233432,"Raw Comment":"2 homozygous individuals (1 pt): 1 patient reported in PMID: 10233432 and 1 unpublished individual based on internal laboratory data meet criteria for PM3.","Number of Patients":1,"In trans Variants":["homozygous c.1702T>C p.(Cys568Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA229471","Variant Name":"NM_000277.2:c.183C>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":10234516,"Raw Comment":"N61K (c.183C>G) detected in 2 patients: Genotypes N61K\/IVS1nt5, and N61K\/R176L (VarID631, Pathogenic).","Number of Patients":2,"In trans Variants":["IVS1nt5","p.R176L c.(527G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229398","Variant Name":"NM_000277.2:c.1217T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":10234516,"Raw Comment":"Seen in trans with I65T (VarID 636, pathogenic) in a patient with mild PKU.","Number of Patients":1,"In trans Variants":["p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229466","Variant Name":"NM_000277.2:c.175G>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":10234516,"Raw Comment":"Patient genotype: D59Y\/A403V","Number of Patients":1,"In trans Variants":["p.A403V c.(1208C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA286505","Variant Name":"NM_000277.2:c.506G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":10234516,"Raw Comment":"Detected with p.P281L (Pathogenic in ClinVar).","Number of Patients":1,"In trans Variants":["p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020919","Variant Name":"NM_000277.3:c.1027T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":10356314,"Raw Comment":"Seen in two individuals with late-diagnosed PKU, in trans with R158Q (Var ID=587) and E280K (Var ID=580), both pathogenic in ClinVar.","Number of Patients":2,"In trans Variants":["p.E280K c.(838G>A)","p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA251545","Variant Name":"NM_001354304.2:c.914_1199+1del","Condition":"phenylketonuria","Criterion":"PM3","PMID":10472529,"Raw Comment":"It has been previously reported in one case with mild PKU (per abnormal blood Phe levels; BH4 deficiency does not appear to have been formally excluded) (PP4), in confirmed trans with the p.E390G variant (Likely Pathogenic per PAH VCEP) (PMID: 10472529) (PM3).","Number of Patients":1,"In trans Variants":["p.E390G c.(1169A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA251530","Variant Name":"NM_000277.2:c.473G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":10479481,"Raw Comment":"Patient genotype: G218V (interpretation not provided) \/R158Q","Number of Patients":1,"In trans Variants":["p.G218V c.(653G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA114367","Variant Name":"NM_000277.1:c.1169A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":10479481,"Raw Comment":"compound heterozygosity: L333F (VarID624, Pathogenic)\/ E390G","Number of Patients":1,"In trans Variants":["p.L333F c.(997C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229676","Variant Name":"NM_000277.1:c.653G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":10479481,"Raw Comment":"2 patients with G218V, 1 in trans with R158Q (Pathogenic in ClinVar, VarID 587), another in trans with I65T (VarID 636, pathogenic\/likely pathogenic in ClinVar).","Number of Patients":2,"In trans Variants":["p.R158Q c.(473G>A)","p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229484","Variant Name":"NM_000277.1:c.202A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":10495930,"Raw Comment":"R68G was detected in trans with R243Q (VarID 591, Pathogenic in ClinVar) in two siblings with mild PKU. Mendelian inheritance was confirmed.","Number of Patients":2,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229579","Variant Name":"NM_000277.2:c.493G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":10598814,"Raw Comment":"Patient genotype: IVS10\/A165T","Number of Patients":1,"In trans Variants":["IVS10"],"labels":"fine-tune"},{"CinGen ID":"CA267677","Variant Name":"NM_000277.2:c.837del","Condition":"phenylketonuria","Criterion":"PM3","PMID":10598814,"Raw Comment":"The c.837del frameshift variant was observed in trans with the pathogenic variant Val388Met (ClinVar 619, Pathogenic).","Number of Patients":1,"In trans Variants":["p.Val388Met c.(1162G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA399805793","Variant Name":"NM_000419.4:c.526C>G","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":10607701,"Raw Comment":"A homozygous proband was reported in PMID: 10607701. Additionally, this variant has been reported in trans with Ile405Thr and Arg977Ter (not included in this assessment to avoid circularity).","Number of Patients":1,"In trans Variants":["homozygous c.526C>G p.(Pro176Ala)"],"labels":"fine-tune"},{"CinGen ID":"CA399805789","Variant Name":"NM_000419.5:c.527C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":10607701,"Raw Comment":"PMID: 10607701 Patient Chinese-14 is compound heterozygous for Pro176Leu and pathogenic variant c.1545-1del, without confirmation of trans phase.","Number of Patients":1,"In trans Variants":["c.1545-1del"],"labels":"fine-tune"},{"CinGen ID":"CA127025","Variant Name":"NM_004004.5:c.235delC","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":10633133,"Raw Comment":"This is a mutation analysis for Japanese non-syndromic hearing loss. The c.235delC variant was identified in 7 affected families. Two families were homozygous, three families were compound het for Y136X, and two families were compound het for R143W.","Number of Patients":7,"In trans Variants":["p.R143W c.(427C>T)","homozygous c.235delC p.(Leu79Cysfs*3)","p.Y136X"],"labels":"fine-tune"},{"CinGen ID":"CA229878","Variant Name":"NM_000277.3:c.969+1G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":10679941,"Raw Comment":"The PAH variant c.969+1G>A (IVS9+1G>A) was reported with the PAH pathogenic variant c.1222C>T (p.Arg408Trp) (ClinVar ID: 577) in a European patient with classical PKU (serum Phe levels above 1200\u00ce\u00bcmol\/L). Cofactor deficiency was excluded by the BH4 test PM3 Points: 1*0.5= 0.5 (PMID: 10679941)","Number of Patients":1,"In trans Variants":["c.1222C>T p.Arg408Trp"],"labels":"fine-tune"},{"CinGen ID":"CA229287","Variant Name":"NM_000277.2:c.1030G>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":10679941,"Raw Comment":"Detected with IVS12+1G>A, pathogenic in Clinvar, Var ID: 576. Parental analysis not reported. PMID: 10679941","Number of Patients":1,"In trans Variants":["IVS12+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229509","Variant Name":"NM_000277.2:c.2T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":10679941,"Raw Comment":"The variant has been previously reported in 2 unrelated probands with classic PKU, in trans with the known pathogenic p.R408W allele (PMID: 10679941).","Number of Patients":2,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229561","Variant Name":"NM_000277.2:c.464G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":10679941,"Raw Comment":"Detected in trans with R408W","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229641","Variant Name":"NM_000277.2:c.59A>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":10679941,"Raw Comment":"This variant was detected in trans with a splicing variant (c.1315+1G>A) in a patient with hyperphenylalaninemia (HPA). The splicing mutation occurs in a canonical exon1-intron1 junction, and is predicted to disrupt the normal function of PAH. It is pathogenic in ClinVar (VarID 576)","Number of Patients":1,"In trans Variants":["c.1315+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA132727","Variant Name":"NM_000441.1:c.349C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":10700480,"Raw Comment":"57 EVA patients screened for SLC26A4. Found in one patinet with HL and EVA but a normal perchlorate test. Did not note a second variant. Variant was absent from 100 control chromosomes-no family\/race info","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA252231","Variant Name":"NM_206933.4:c.956G>A","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":10729113,"Raw Comment":"1 proband homozygous.","Number of Patients":1,"In trans Variants":["homozygous c.956G>A p.(Cys319Tyr)"],"labels":"fine-tune"},{"CinGen ID":"CA229775","Variant Name":"NM_000277.1:c.805A>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":10767174,"Raw Comment":"The genotype combination of an I269L allele with a classic PKU allele (R261X) was associated with a non-PKU hyperphenylalaninemia phenotype. (VarID 610, Pathogenic).","Number of Patients":1,"In trans Variants":["p.R261X"],"labels":"fine-tune"},{"CinGen ID":"CA229358","Variant Name":"NM_000277.3:c.1132A>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":10767174,"Raw Comment":"Mild PKU Patient F15 of PMID: 10767174 is compound heterozygous for Thr378Ser and Arg243Gln (ClinVar 591; Pathogenic). Confirmation of phase was not reported. 0.5pt","Number of Patients":1,"In trans Variants":["p.Arg243Gln c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA251544","Variant Name":"NM_000277.2:c.194T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":10767174,"Raw Comment":"F13 and G3: I65T\/P281L; G21: I65T\/IVS10nt-11; G62: I65T\/R252W; F38: I65T\/I65T; F27: I65T\/R243Q.","Number of Patients":5,"In trans Variants":["c.IVS10nt-11","p.P281L c.(842C>T)","p.R243Q c.(728G>A)","homozygous c.194T>C p.(Ile65Thr)","p.R252W c.(754C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA400024958","Variant Name":"NM_000212.3:c.863T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":10891446,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. For one of those individuals, one was compound heterozygous for this variant and a pathogenic variant, c.847_848del (p.Ala283IlefsTer12), confirmed in trans by family testing, (CAID:CA8623068, PMID:10891446).","Number of Patients":1,"In trans Variants":["[\"c.847\\_848del p.Ala283IlefsTer12\"]"],"labels":"fine-tune"},{"CinGen ID":"CA278713","Variant Name":"NM_000260.4(MYO7A):c.6560G>A","Condition":"Usher syndrome","Criterion":"PM3","PMID":10930322,"Raw Comment":"Found presumed in trans with p.Glu968Asp (a two star pathogenic variant in clinvar). 0.5 points.","Number of Patients":1,"In trans Variants":["p.Glu968Asp c.(2904G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA6264590","Variant Name":"NM_000051.3:c.332-1G>A","Condition":"hereditary breast cancer","Criterion":"PM3-Strong","PMID":10980530,"Raw Comment":"This variant has been observed in a compound heterozygous state (confirmed) in one individual with Ataxia-Telangiectasia (PMID: 10980530 PM3) (4 POINTS)\n","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA127025","Variant Name":"NM_004004.5:c.235delC","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":10983956,"Raw Comment":"147 Korean patients with NSHL were screened for variants in GJB2. The c.235delC variant was identifed in 5 homozygous individuals and 5 compound hets. Because the het individuals did not have a second variant listed, I would only count the homozygous individuals here.","Number of Patients":10,"In trans Variants":["homozygous c.235delC p.(Leu79Cysfs*3)"],"labels":"fine-tune"},{"CinGen ID":"CA915940464","Variant Name":"NM_000419.4:c.291del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":11091187,"Raw Comment":"One homozygous proband has been reported in PMID: 11091187. 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.291del p.(Ser98Argfs*13)"],"labels":"fine-tune"},{"CinGen ID":"CA631044684","Variant Name":"NM_000156.6:c.571-3C>G","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3","PMID":11136556,"Raw Comment":"Identified in one individual with GAMT deficiency who was a comp het for c.491insG (paternal) (ClinVar path, including by CCDS VCEP, ID 495685) \/c.571-3C>G (maternal) (PMID: 11136556)","Number of Patients":1,"In trans Variants":["c.491insG"],"labels":"fine-tune"},{"CinGen ID":"CA16020974","Variant Name":"NM_001354304.2:c.1232C>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":11139255,"Raw Comment":"detected with V388M (P by multiple submitters) PMID: 11139255","Number of Patients":0,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229329","Variant Name":"NM_000277.2:c.1069T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":11139255,"Raw Comment":"Seen in an individual with classic PKU, in trans with R176X (pathogenic). PHE level >4 for all patients in study.","Number of Patients":1,"In trans Variants":["p.R176X"],"labels":"fine-tune"},{"CinGen ID":"CA229715","Variant Name":"NM_000277.2:c.719T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":11139255,"Raw Comment":"F240S seen in trans with R261Q (VarID 582, Pathogenic\/Likely Pathogenic). IVS2+19T>C polymorphism (VarID 92736, benign) occurred in cis to the F240S mutation, as the mother had these substitutions in the same status.","Number of Patients":1,"In trans Variants":["p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA273357","Variant Name":"NM_000277.1:c.721C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":11142755,"Raw Comment":"R241C seen in 2 Japanese MHP patients in trans with R413P (VarID 592, Pathogenic in ClinVar) and R243Q (VarID 591, Pathogenic in ClinVar).","Number of Patients":2,"In trans Variants":["p.R413P c.(1238G>C)","p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229379","Variant Name":"NM_000277.1:c.1197A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":11214902,"Raw Comment":"phenylketonuria (PKU) patient compound heterozygous for c.1197A\/T and R408W (paternal allele). R408W (varID 577) is Pathogenic in ClinVar (9 submitters)","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA6748985","Variant Name":"NM_000277.2:c.299A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":11244681,"Raw Comment":"H100R detected with IVS10.","Number of Patients":1,"In trans Variants":["IVS10"],"labels":"fine-tune"},{"CinGen ID":"CA229576","Variant Name":"NM_000277.2:c.490A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":11244681,"Raw Comment":"Detected with D145V (VarID 102667, Pathogenic).","Number of Patients":1,"In trans Variants":["p.D145V c.(434A>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229297","Variant Name":"NM_000277.3:c.1043_1053del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":11328945,"Raw Comment":"PMID: 11328945 - L348fs detected with R408W, reported as Pathogenic in ClinVar (VarID:577, 21 submitters), phase not confirmed - 0.5 points","Number of Patients":"NA","In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229500","Variant Name":"NM_000277.2:c.250G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":11328945,"Raw Comment":"Maternal PAH genotype: F39L\/D84Y (VarID605, pathogenic)","Number of Patients":1,"In trans Variants":["p.F39L c.(115T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA117001","Variant Name":"NM_001033855.3:c.241C>T","Condition":"severe combined immunodeficiency due to DCLRE1C deficiency","Criterion":"PM3-Supporting","PMID":11336668,"Raw Comment":"One proband (P2) is homozygous (Table 1) for this variant (0.5pt; PM3_Supporting). PMID: 11336668","Number of Patients":1,"In trans Variants":["homozygous c.241C>T p.(Arg81*)"],"labels":"fine-tune"},{"CinGen ID":"CA273111","Variant Name":"NM_000277.1:c.508C>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":11385716,"Raw Comment":"H170D was present in 2 Hispanics whose genotypes were H170D\/H170D and H170D\/R261X.","Number of Patients":2,"In trans Variants":["p.H170D c.(508C>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229757","Variant Name":"NM_000277.1:c.781C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":11385716,"Raw Comment":"Patient genotype: H170D (VarID 92744, Pathogenic) \/R261X","Number of Patients":1,"In trans Variants":["p.H170D c.(508C>G)"],"labels":"fine-tune"},{"CinGen ID":"CA251529","Variant Name":"NM_000277.1:c.754C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":11524738,"Raw Comment":"Patient 10 genotype: R261Q (VarID 582 P\/LP) \/R252W. Patient 28: IVS12nt1 (VarID 576, P) \/R252W. Patient 42: R252W\/R68S (VarID 92738, P\/LP).","Number of Patients":3,"In trans Variants":["p.R261Q c.(782G>A)","IVS12nt1","p.R68S c.(204A>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229666","Variant Name":"NM_000277.1:c.631C>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":11708866,"Raw Comment":"R261Q\/P211T (VarID582, Pathogenic\/Likely Pathogenic)","Number of Patients":1,"In trans Variants":["p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA8623016","Variant Name":"NM_000212.3:c.655G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":11722423,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. For one of those individuals, one was compound heterozygous for this variant and a pathogenic variant c.602delA, confirmed in trans by cloning and sequencing of PCR amplified cDNA (PMID:11722423). Total points: 1 (PM3).","Number of Patients":1,"In trans Variants":["c.602delA p.(Asn201Thrfs*6)"],"labels":"fine-tune"},{"CinGen ID":"CA400032927","Variant Name":"NM_000212.3:c.1955A>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":11798398,"Raw Comment":"Patient Ssyl (PMID: 11798398) was homozygous for this variant (PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.1955A>T p.(His652Leu)"],"labels":"fine-tune"},{"CinGen ID":"CA399802478","Variant Name":"NM_000419.5:c.1591C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":11798398,"Raw Comment":"Patient NA (PMID: 11798398) is homozygous for this variant (PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.1591C>T p.(Gln531*)"],"labels":"fine-tune"},{"CinGen ID":"CA399794666","Variant Name":"NM_000419.5:c.2540T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":11798398,"Raw Comment":"Patient FC (PMID: 11798398) was homozygous for this variant (PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.2540T>C p.(Leu847Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA399791378","Variant Name":"NM_000419.5:c.2842-1G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":11798398,"Raw Comment":"MMc (PMID: 11798398) is homozygous for this variant (PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.2842-1G>C "],"labels":"fine-tune"},{"CinGen ID":"CA8603182","Variant Name":"NM_000419.4:c.1234G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Strong","PMID":11798398,"Raw Comment":"Patient FO is compound heterozygous for the Pathogenic variant c.2153dupG (p.Cys718Trpfs*2) and c.1234G>A (p.Gly412Arg). The trans phase of the variants was not confirmed. 0.5pt","Number of Patients":1,"In trans Variants":"[\"c.2153dupG p.Cys718Trpfs*2\"]","labels":"fine-tune"},{"CinGen ID":"CA915940801","Variant Name":"NM_000419.5:c.3061-6C>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":11798398,"Raw Comment":"TG (PMID: 11798398) is homozygous for this variant 0.5pt\t","Number of Patients":1,"In trans Variants":["homozygous c.3061-6C>G "],"labels":"fine-tune"},{"CinGen ID":"CA399805465","Variant Name":"NM_000419.5:c.666C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":11798398,"Raw Comment":"Patient CC (PMID: 11798398) was homozygous for this variant (PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.666C>A p.(Phe222Leu)"],"labels":"fine-tune"},{"CinGen ID":"CA281520","Variant Name":"NM_000277.1:c.-4165_-407del","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":11935335,"Raw Comment":"The parenthood of the proband was confirmed by DNA fingerprinting. By linkage analysis to the c.1155G\/C (L385L) polymorphic marker, the c.227A\u00e2\u0086\u0092G substitution was deduced to be inherited from the father. Thus, the E76G mutation was most likely a de novo mutation that had occurred during spermatogenesis. In addition to proband BF of family W, probands of two other families, X and AU, were also found to carry this deletion and were both compound heterozygote\nwith the other allele carrying the R408Q mutation.","Number of Patients":3,"In trans Variants":["p.R408Q c.(1223G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA399804480","Variant Name":"NM_000419.5:c.1096C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":12083483,"Raw Comment":"Patient CT of PMID: 12083483 is homozygous for the Arg366Ter nonsense variant. 0.5pt","Number of Patients":1,"In trans Variants":["p.Arg366Ter c.(1096C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA399805147","Variant Name":"NM_000419.5:c.800G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":12083483,"Raw Comment":"Patient DRP of PMID: 12083483 is compound heterozygous for ariant c.2930del (classified Pathogenic by the Platelet Disorders VCEP) and Gly267Glu (confirmation of trans phase not reported). 0.5pt","Number of Patients":1,"In trans Variants":["c.2930del p.(Arg977Glnfs*?)"],"labels":"fine-tune"},{"CinGen ID":"CA399805793","Variant Name":"NM_000419.4:c.526C>G","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":12083483,"Raw Comment":"Patient MR is compound heterozygous for the Ile405Thr (reported as Ile374Thr) variant and Pro176Ala (reported as Pro145Ala). The variants were reported to have been confirmed to be in the trans phase. This variant is used as evidence to support PM3 for Ile405Thr, as such it is not used here to avoid a circular argument.","Number of Patients":1,"In trans Variants":["p.Ile405Thr c.(1214T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA915940767","Variant Name":"NM_000419.5:c.2555del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":12083483,"Raw Comment":"Patient VA of PMID: 12083483 is homozygous for c.2555del 0.5pt\t","Number of Patients":1,"In trans Variants":["homozygous c.2555del p.(Gln852Argfs*58)"],"labels":"fine-tune"},{"CinGen ID":"CA8622899","Variant Name":"NM_000212.2:c.224del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":12083483,"Raw Comment":"Patient MR is homozygous for c.224del.","Number of Patients":1,"In trans Variants":["homozygous c.224del p.(Cys75Leufs*10)"],"labels":"fine-tune"},{"CinGen ID":"CA290950815","Variant Name":"NM_000419.4:c.1214T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":12083483,"Raw Comment":"Patient MR is compound heterozygous for the Ile405Thr (reported as Ile374Thr) variant and Pro176Ala (reported as Pro145Ala). The variants were reported to have been confirmed to be in the trans phase. Pro176Ala has been classified as Pathogenic by the ClinGen Platelet Disorders VCEP. 1pt","Number of Patients":1,"In trans Variants":["p.Pro176Ala c.(526C>G)"],"labels":"fine-tune"},{"CinGen ID":"CA8602816","Variant Name":"NM_000419.4:c.2113T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":12083483,"Raw Comment":"Three GT patients were identified to have the Cys705Arg variant. Patient BM was heterozygous for this variant, however the second variant was not identified in this patient. Patients CE and LRI were both homozygous for Cys705Arg.","Number of Patients":3,"In trans Variants":["homozygous c.2113T>C p.(Cys705Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA400029958","Variant Name":"NM_000212.2:c.1595G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":12353082,"Raw Comment":"The variant has been reported once in a homozygous state, in Patient 1 whose parents are first cousins.","Number of Patients":1,"In trans Variants":["homozygous c.1595G>A p.(Cys532Tyr)"],"labels":"fine-tune"},{"CinGen ID":"CA915940804","Variant Name":"NM_000212.3:c.122_125dup","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":12353082,"Raw Comment":"One GT patient has been identified with this homozygous variant in PMID: 12353082 (Patient 2).","Number of Patients":1,"In trans Variants":["homozygous c.122_125dup p.(Cys42*)"],"labels":"fine-tune"},{"CinGen ID":"CA229395","Variant Name":"NM_000277.2:c.1200-8G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":12409276,"Raw Comment":"Patients 7.1 and 7.2 genotype: IVS11-8G>A\/IVS10-11G>A. Parental confirmation not reported.","Number of Patients":2,"In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA6748814","Variant Name":"NM_000277.1:c.859C>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":12409276,"Raw Comment":"Single patient in trans with P281L, classic PKU","Number of Patients":1,"In trans Variants":["p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA8602816","Variant Name":"NM_000419.4:c.2113T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":12424194,"Raw Comment":"Patient C is compound heterozygous for the Ile405Thr (reported as Ile374Thr) variant derived from the mother and the Cys705Arg (reported as Cys674Arg) from the father. This Cys705Arg variant can be used in the assessment ofIle405Thr so will not be used here to avoid a circular argument.","Number of Patients":1,"In trans Variants":["p.Ile405Thr c.(1214T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA290950815","Variant Name":"NM_000419.4:c.1214T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":12424194,"Raw Comment":"Patient C is compound heterozygous for the Ile405Thr (reported as Ile374Thr) variant derived from the mother and the Pathogenic variant Cys705Arg (reported as Cys674Arg) from the father. 1pt","Number of Patients":1,"In trans Variants":["p.Cys674Arg","p.Ile374Thr"],"labels":"fine-tune"},{"CinGen ID":"CA114364","Variant Name":"NM_000277.1:c.1243G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":12501224,"Raw Comment":"Patient 4: F39L (VarID 605, Pathogenic)\/D415N; Patient 5:Y414C (VarID 593, Pathogenic)\/D415N.","Number of Patients":2,"In trans Variants":["p.F39L c.(115T>C)","p.Y414C c.(1241A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229609","Variant Name":"NM_000277.2:c.529G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":12501224,"Raw Comment":"Patient 9 genotype: V177M\/R408W","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA251544","Variant Name":"NM_000277.2:c.194T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":12501224,"Raw Comment":"Patient 24 Genotype: I65T\/Y414C","Number of Patients":1,"In trans Variants":["p.Y414C c.(1241A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA267684","Variant Name":"NM_000277.2:c.912+2T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":12655552,"Raw Comment":"With respect to the published literature, it has been previously reported in one Croatian proband with \u00e2\u0080\u009csevere\u00e2\u0080\u009d PKU (defined as serum Phe levels >1200); BH4 deficiency does not appear to have been formally excluded (PMID: 12655552) (PP4). The variant was found as a single (heterozygous) variant with the known pathogenic p.R408W allele (see ClinVar variant ID 577) (PM3); phase was confirmed via parental testing.","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229396","Variant Name":"NM_000277.3:c.1204T>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":12655552,"Raw Comment":"PMID: 12655552 - F402L detected with c.1169A>G (p.Glu390Gly) in 1 Croatian patient, reported as Pathogenic in ClinVar, VarID: 625, phase unknown - 0.5 points","Number of Patients":1,"In trans Variants":["c.1169A>G p.Glu390Gly"],"labels":"fine-tune"},{"CinGen ID":"CA220582","Variant Name":"NM_000277.2:c.355C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":12655554,"Raw Comment":"in trans with IVS2+1G>A","Number of Patients":"NA","In trans Variants":["IVS2+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":12676893,"Raw Comment":"This study identified a deaf Korean proband who was heterozygous for the variant. No other allele was reported. This cannot be added as support for PM3 but may be useful information.","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":12788906,"Raw Comment":"Total: 2 comp het probands with Path variants in trans and 2 homzygous probands. This paper identified 4 families who had the p.Val138Phe identified with disease. The variant was present in a homozygous individual with Pendred syndrome in family A and segregated from two unaffected nonconsanguineous Turkish parents who were het carriers. Family B (German nonconsanguineous): Father had the p.Y530H (Path in GI) variant, mother had the p.V138F variant, 2 affected compound het children. Family C (German nonconsanguineous), Father and sister were affected by Pendred syndrome and had the p.V138F and E384G variants, but his p.E384G (Path in GI) heterozygous son was unaffected. Family D (German nonconsanguineous): Pendred syndrome in homozygous p.V138F German boy who had heterozygous mother, aunt and uncle.","Number of Patients":6,"In trans Variants":["p.V138F c.(412G>T)","p.Y530H c.(1588T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA8603528","Variant Name":"NM_000419.5:c.188G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":12871379,"Raw Comment":"This variant has been detected in homozygosity in at least 1 proband with Glanzmann thrombasthenia. Parents were heterozygous. (0.5pts, PMID: 12871379). Total points: 0.5 (PM3_Supporting).\n","Number of Patients":1,"In trans Variants":["homozygous c.188G>A p.(Arg63Lys)"],"labels":"fine-tune"},{"CinGen ID":"CA341585","Variant Name":"NM_000162.5:c.1133C>T","Condition":"monogenic diabetes","Criterion":"PM3-Supporting","PMID":14578306,"Raw Comment":"This variant has been detected in an individual with neonatal diabetes who was homozygous for this variant and had negative antibodies (PM3_Supporting, PMID: 14578306)","Number of Patients":1,"In trans Variants":["homozygous c.1133C>T p.(Ala378Val)"],"labels":"fine-tune"},{"CinGen ID":"CA229570","Variant Name":"NM_000277.2:c.472C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":14681498,"Raw Comment":"In case 2, P407S (VarID102568, clinical significance not provided) was detected in one allele and R158W in the other allele.","Number of Patients":1,"In trans Variants":["p.P407S c.(1219C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229826","Variant Name":"NM_000277.2:c.856G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":14722928,"Raw Comment":"Two independent patients reported, one in trans with R243Q and classic PKU, and one in trans with R241C and mild PKU","Number of Patients":2,"In trans Variants":["p.R243Q c.(728G>A)","p.R241C c.(721C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229863","Variant Name":"NM_000277.1:c.940C>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":14722928,"Raw Comment":"Taiwanese population, novel mutation in this paper. Single patient with 185uM phe at dx.","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229404","Variant Name":"NM_000277.1:c.1223G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":14722928,"Raw Comment":"Patient 5: IVS4-1G>A (VarID102671, P\/LP)+ R408Q. Patient 6: E6nt-96A>G (VarID590? P\/LP)+ R408Q. Patients 17 + 18: R241C (VarID102803, P)+ R408Q.","Number of Patients":4,"In trans Variants":["IVS4-1G>A","E6nt-96A>G","p.R241C c.(721C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229775","Variant Name":"NM_000277.1:c.805A>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":14726806,"Raw Comment":"E280K (VarID 580, Pathogenic)\/I269L","Number of Patients":1,"In trans Variants":["p.E280K c.(838G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA406175434","Variant Name":"NM_014297.5:c.505+1G>T","Condition":"ethylmalonic encephalopathy","Criterion":"PM3-Supporting","PMID":14732903,"Raw Comment":"4 homozygotes in literature, 1 in Tiranti et al 2004, 2 in Mineri et al 2008, 1 in Dweikat et al no parental testing so unable to score. Only Tiranti et al 2004 reported linkage studies confirming in trans. Utilized ClinGen SVI v.10 scoring guidelines for PM3 TOTAL = 0.5 (Homozygote confirmed in trans; PMID 14732903)","Number of Patients":1,"In trans Variants":["homozygous c.505+1G>T "],"labels":"fine-tune"},{"CinGen ID":"CA401361056","Variant Name":"NM_000152.5:c.399C>A","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":14972326,"Raw Comment":"Proband 1 has infantile onset Pompe disease and is homozygous for c.399C>A (p.Tyr133X*); both parents are confirmed to be heterozygous for the variant. The patient has no detectable GAA activity in cultured fibroblasts (PMID 14972326), meeting PP4. This data was awarded 0.5 points based on the specifications of the ClinGen LSD VCEP.","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA626684863","Variant Name":"NM_000212.3:c.1406dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":14985172,"Raw Comment":"Patient 2 of PMID: 14985172 is homozygous with parents confirmed carriers (0.5pt; PM3_supporting).\t","Number of Patients":1,"In trans Variants":["homozygous c.1406dup p.(Asn470*)"],"labels":"fine-tune"},{"CinGen ID":"CA172240","Variant Name":"NM_004004.5:c.71G>A","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":15070423,"Raw Comment":"W24* was found in trans with GJB2 35delG variant in one deaf individual. Also found in trans in unaffected individuals with R127H variant.","Number of Patients":2,"In trans Variants":["35delG p.(Gly12Valfs*2)","R127H c.(380G>A)"],"labels":"eval"},{"CinGen ID":"CA16608466","Variant Name":"NM_000419.4:c.2944G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":15099289,"Raw Comment":"The proband was described to have triple heterozygosity with a maternally inherited pathogenic splice variant, c.1946+1G>A, in trans with both Val982Met and Ala958Thr, inherited paternally. However it was asserted that Ala989Thr was a polymorphism and Val982Met is the second variant of interest in this patient. 1pt","Number of Patients":1,"In trans Variants":["c.1946+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA402998035","Variant Name":"NM_138924.3:c.160G>C","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":15108290,"Raw Comment":"Identified in one homozygous proband, in cis with two benign variants (c.626C>T (p.Thr209Met) (ClinVar ID: 21068) and c.459+71G>A (ClinVar ID: 21067)) (PMID: 15108290) (0.5pts). ","Number of Patients":1,"In trans Variants":["c.626C>T (p.Thr209Met)","c.459+71G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16020911","Variant Name":"NM_000277.1:c.970A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":15159646,"Raw Comment":"Single patient c.[(970A>G)];[(441+5G>T)] (pathogenic in clinvar). Phase determined via parental studies","Number of Patients":1,"In trans Variants":["c.441+5G>T"],"labels":"fine-tune"},{"CinGen ID":"CA262054","Variant Name":"NM_206933.2:c.1036A>C","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":15241801,"Raw Comment":"detected in trans with p.Trp409X","Number of Patients":1,"In trans Variants":["p.Trp409X"],"labels":"fine-tune"},{"CinGen ID":"CA399795582","Variant Name":"NM_000419.5:c.2449-1G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":15293575,"Raw Comment":"This variant was identified in a patient with GT type I in the homozygous state (PMID 15293575).","Number of Patients":1,"In trans Variants":["homozygous c.2449-1G>C "],"labels":"fine-tune"},{"CinGen ID":"CA252228","Variant Name":"NM_007123.5:c.4338_4339delCT","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":15325563,"Raw Comment":"This study also identified 2 USH2 patients with the Cys1447fs variant in trans with the C759F variant which is classified as pathogenic by the LMM in ClinVar. There was also a homzygote. The variant was also identified in a heterozygous state in 4 cases of autosomal recessive RP but these patients didn't appear to have any other USH2A mutations.","Number of Patients":2,"In trans Variants":["p.C759F c.(2276G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":15355436,"Raw Comment":"This study identified 3 French probands with Pendred syndrome and the variant. 2 compound het, both with p.Y530H in trans, and one homozygous p.T410M. p.Y530H is a pathogenic\/LPvaraint in ClinVar (LMM: path). Therefore this would count as 2.5 points for PM3 counts.","Number of Patients":3,"In trans Variants":["p.Y530H c.(1588T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229500","Variant Name":"NM_000277.2:c.250G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":15503242,"Raw Comment":"When available, parental DNA samples were sequenced to confirm trans configurations in compound heterozygotes and to distinguish homozygosity from hemizygosity. Patient 38: PAH allele 1 D84Y; PAH allele 2 Y356X (VarID 595, P\/LP)","Number of Patients":1,"In trans Variants":["p.Y356X"],"labels":"fine-tune"},{"CinGen ID":"CA16020867","Variant Name":"NM_000277.1:c.833C>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":15503242,"Raw Comment":"Found in trans with IVS4 (Variant ID 594) which is pathogenic in Clinvar.","Number of Patients":1,"In trans Variants":["IVS4"],"labels":"fine-tune"},{"CinGen ID":"CA220589","Variant Name":"NM_000277.1:c.842C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":15503242,"Raw Comment":"Table 1 showed two patients with either moderate (IVS4-1G>A and P281L) or classical PKU (G239S and P281L).","Number of Patients":2,"In trans Variants":["p.G239S c.(715G>A)","IVS4-1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA251526","Variant Name":"NM_000277.2:c.331C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":15503242,"Raw Comment":"Patient 29: R111X\/R243Q (VarID591, Pathogenic)","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229855","Variant Name":"NM_000277.1:c.929C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":15503242,"Raw Comment":"Molecular basis of PKU in Korean population. 79 unrelated families. Urinary pterin analysis and DHPR assays performed to exclude BH4 defect. Single patient with moderate PKU (600-1200umol\/L) IVS4-1G>A (pathogenic) \/ S310F.","Number of Patients":1,"In trans Variants":["IVS4-1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229291","Variant Name":"NM_000277.2:c.1033G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":15503242,"Raw Comment":"Found in trans with R243Q (pathogenic in ClinVar) in Patients 53 and 65, and G332V (not in ClinVar).","Number of Patients":3,"In trans Variants":["p.G332V c.(995G>T)","p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA16020790","Variant Name":"NM_000277.3:c.443G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":15589814,"Raw Comment":"Detected with IVS4nt5G>T (c.441+5G>T) pathogenic 5 submitters PMID: 15589814","Number of Patients":"NA","In trans Variants":["IVS4nt5G>T c.441+5G>T"],"labels":"fine-tune"},{"CinGen ID":"CA229679","Variant Name":"NM_000277.1:c.665A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":15589814,"Raw Comment":"D222G found in trans with R408W (VarID 577, pathogenic in ClinVar) in 1 PKU patient","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA400025722","Variant Name":"NM_000212.3:c.989T>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":15634267,"Raw Comment":"The patient in PMID: 15634267 is compound heterozygous for the maternal Ile330Asn and paternal His306Pro (classified Likely Pathogenic by the PD-VCEP) variants (1pt; PM3).","Number of Patients":1,"In trans Variants":["p.His306Pro c.(917A>C)"],"labels":"fine-tune"},{"CinGen ID":"CA10624373","Variant Name":"NM_002185.5:c.83-2A>T","Condition":"severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive","Criterion":"PM3-Supporting","PMID":15661025,"Raw Comment":"P4 of PMID: 15661025 is homozygous for this variant (0.5pt; PM3_supporting). Additional compound heterozygotes have been reported but second variants have not yet been curated.","Number of Patients":1,"In trans Variants":["homozygous c.83-2A>T "],"labels":"fine-tune"},{"CinGen ID":"CA274422","Variant Name":"NM_000441.1:c.365dupT","Condition":"Pendred syndrome","Criterion":"PM3-Supporting","PMID":15679828,"Raw Comment":"The variant was detected in 2 probands. One proband had the c.365insT variant on one allele and the c.1707+5G>A variant on the other allele. This variant is classified as pathogenic in ClinVar by a submission from this publication, but it may not be classified as Likely Pathogenic based on our current criteria. Also, there is one proband with hearing loss and enlarged vestibule who has this variant in a heterozygous state with the wild type. This does not provide support for or against the variant's impact.","Number of Patients":1,"In trans Variants":["c.1707+5G>A"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":15689455,"Raw Comment":"This study identified 2 patients with Pendred syndrome adn one patient with an indeterminate EVA phenotype. The patient with indeterminate phenotype had a c.1343_1344insAGTC variant in trans with the p.V138F variant. One Pendred patient was homozygous for the p.V138F variant and another patient was compound het with a p.E384G variant (P\/LP).","Number of Patients":3,"In trans Variants":["c.1343_1344insAGTC","homozygous c.412G>T p.(Val138Phe)","p.E384G c.(1151A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA134989","Variant Name":"NM_004004.5:c.571T>C","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Supporting","PMID":15700112,"Raw Comment":"60 unrelated Japanese probands underwent GJB2 sequencing. 1 individual homozygous for Phe191Leu identified with mild sloping to profound SNHL. PM3 = 0.5 POINTS. 147 unrelated Japanese hearing controls. Variant not found.","Number of Patients":1,"In trans Variants":["homozygous c.571T>C p.(Phe191Leu)"],"labels":"fine-tune"},{"CinGen ID":"CA399806084","Variant Name":"NM_000419.5:c.399C>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":15717695,"Raw Comment":"This variant was found to be homozygous in the patient in which it was identified (PMID 15717695).","Number of Patients":1,"In trans Variants":["homozygous c.399C>G p.(Asp133Glu)"],"labels":"fine-tune"},{"CinGen ID":"CA400025655","Variant Name":"NM_000212.3:c.961A>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":15748237,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia (Patient 3 in PMID: 15748237). This patient was homozygous for the variant (0.5 points, PM3_Supporting). \n\n\n\n","Number of Patients":1,"In trans Variants":["homozygous c.961A>C p.(Met321Leu)"],"labels":"fine-tune"},{"CinGen ID":"CA915940807","Variant Name":"NM_000212.3:c.812dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":15748237,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. One proband was homozygous for the variant (PMID:15748237). Total points: .5 (PM3_Supporting).\n","Number of Patients":1,"In trans Variants":["homozygous c.812dup p.(Leu271Phefs*7)"],"labels":"fine-tune"},{"CinGen ID":"CA8602531","Variant Name":"NM_000419.4:c.2915dup","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":15748238,"Raw Comment":"The proband in this paper is compound heterozygous for this variant and a splice region variant, c.2602-3C>G, confirmed in trans by sequencing of patient cDNA clones. This proband was not counted here to avoid circularity.","Number of Patients":1,"In trans Variants":["c.2602-3C>G"],"labels":"fine-tune"},{"CinGen ID":"CA376065954","Variant Name":"NM_001033855.3:c.47T>C","Condition":"severe combined immunodeficiency due to DCLRE1C deficiency","Criterion":"PM3-Strong","PMID":15770702,"Raw Comment":"Patient 5 is a compound heterozygous with S119X (Pathogenic according to the SCID VCEP specifications, 1 pt, PM3 Met. PMID: 15770702).\nNot reported in the literature, but this variant was identified in one patient at Invitae with a clinical diagnosis of SCID. In this patient, the variant co-occurred - in trans - confirmed by parental testing - with DCLRE1C deletion (Exons 1-3), pathogenic according to the SCID VCEP specifications: 1 pt.\nTotal: 1+1: 2 pts, PM3_Strong.","Number of Patients":1,"In trans Variants":["p.S119X"],"labels":"fine-tune"},{"CinGen ID":"CA387460990","Variant Name":"NM_004004.5:c.516G>C","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Supporting","PMID":15790391,"Raw Comment":"76 Altaian (South Siberia, Russia) individuals with NSHL were tested for variants in GJB2, GJB6 deletions, and mitochondrial variants. The p.Trp172Cys variant was identified in one individual who was compound het for the c.235delC variant. It was absent from 130 unrelated Altaian controls.","Number of Patients":1,"In trans Variants":["c.235delC p.(Leu79Cysfs*3)"],"labels":"eval"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":15811013,"Raw Comment":"Family from a small village but not known to be consanguineous had 4 affected homozygotes of the T410M mutation but also had a compound heterozygote with the D724G variant. This variant was submitted to ClinVar as pathogenic by the LMM (only ClinVar submission). Therefore this family would provide 1.0 points for PM3 as the compound het case would be the only one scored.","Number of Patients":5,"In trans Variants":["p.T410M c.(1229C>T)","p.D724G c.(2171A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA044260","Variant Name":"NM_000527.5:c.664T>C","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":15823276,"Raw Comment":" Variant meets PM2 and is identified in two index cases with homozygous FH phenotype (LDL mmol\/L = 17.9 and 14.09 respectively), PMID: 15823276","Number of Patients":2,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA915940790","Variant Name":"NM_000419.5:c.1618del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":15886807,"Raw Comment":"GT patient from PMID: 15886807 is homozygous for the c.1618del mutation. Meets PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1618del p.(Gln540Serfs*25)"],"labels":"fine-tune"},{"CinGen ID":"CA286506","Variant Name":"NM_000277.1:c.688G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":15943553,"Raw Comment":"R158Q\/V230I present in one patient with classical PKU (seen with V245V\/IVS3nt-22ct\/IVS5nt-54a>g); G272X\/V230I present in one patient showing HPA phenotype (seen with V245V\/E280 > Q280)","Number of Patients":2,"In trans Variants":["p.V230I c.(688G>A)","p.R158Q c.(473G>A)","p.G272X"],"labels":"fine-tune"},{"CinGen ID":"CA399803370","Variant Name":"NM_000419.5:c.1429G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":15946231,"Raw Comment":"This variant was detected in the homozygous state in a patient with GT (PMID 15946231).","Number of Patients":1,"In trans Variants":["homozygous c.1429G>C p.(Ala477Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA229516","Variant Name":"NM_000277.3:c.329C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":16051511,"Raw Comment":"Observed with c.842C>T (p.Pro281Leu) (Likely pathogenic by PAH VCEP variation ID: 589), confirmed in trans (PMID: 16051511).","Number of Patients":1,"In trans Variants":["c.842C>T p.Pro281Leu"],"labels":"fine-tune"},{"CinGen ID":"CA172208","Variant Name":"NM_004004.5:c.107T>C","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":16125251,"Raw Comment":"Of 65 nonsyndromic pediatric cochlear implant patients with severe to profound hearing loss, the p.L36P variant was found in one African proband in trans with the 35delG variant. Four total African ethnicity probands were included in this study.","Number of Patients":1,"In trans Variants":["35delG"],"labels":"fine-tune"},{"CinGen ID":"CA6748814","Variant Name":"NM_000277.1:c.859C>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":16198137,"Raw Comment":"Single patient with MHP, in trans with A300S","Number of Patients":1,"In trans Variants":["p.A300S c.(898G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229643","Variant Name":"NM_000277.1:c.601C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":16198137,"Raw Comment":"Patient 44 Genotype H201Y\/R158Q (VarID 587, Pathogenic in ClinVar)","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229794","Variant Name":"NM_000277.2:c.826A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":16198137,"Raw Comment":"Two patients, both in trans with pathogenic variants (A300S and R261Q)","Number of Patients":2,"In trans Variants":["p.R261Q c.(782G>A)","p.A300S c.(898G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229431","Variant Name":"NM_000277.3:c.1315+6T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":16256386,"Raw Comment":"This variant was documented in one Northern Chinese patient with mild PKU, with the pathogenic PAH variant Arg413Pro in trans (PMID: 16256386). It was not specified whether parental analysis was performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["p.Arg413Pro c.(1238G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229342","Variant Name":"NM_000277.3:c.1099dup","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":16256386,"Raw Comment":"The patient reported in PMID: 16256386 is reported compound heterozygous for c.1099dup and R243Q (ClinVar 591, Pathogenic by multiple submitters). Confirmation of trans phase was not reported. 0.5pt","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229841","Variant Name":"NM_000277.2:c.907T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":16256386,"Raw Comment":"Identified in a single patient with classic PKU, BH4 defect not excluded, in trans with D282G.","Number of Patients":1,"In trans Variants":["p.D282G c.(845A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229583","Variant Name":"NM_000277.2:c.498C>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":16256386,"Raw Comment":"Genotypes: R111X (P, 7 submitters)+ Y166X, Y166X + IVS4+1G>A (P\/LP, 4 submitters), Y166X + Y204C (P\/LP, 4 submitters), Y166X + Y356X (c.1068C>A P, 5 submitters), Y166X + V399V (P, 5 submitters)","Number of Patients":14,"In trans Variants":["p.Y204C c.(611A>G)","p.Y356X","p.R111X","IVS4+1G>A","p.V399V"],"labels":"fine-tune"},{"CinGen ID":"CA229346","Variant Name":"NM_000277.2:c.1101G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":16256386,"Raw Comment":"In trans with R243Q. Maternal or paternal inheritance of mutations was determined particularly for patients with novel mutation when parental DNA was available. PMID: 16256386","Number of Patients":"NA","In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229769","Variant Name":"NM_000277.2:c.799C>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":16256386,"Raw Comment":"Patient genotype: Q267E + R111X (VarID 581, Pathogenic). Maternal or paternal inheritance of mutations was determined particularly for patients with novel mutation when parental DNA was available.","Number of Patients":1,"In trans Variants":["p.R111X"],"labels":"fine-tune"},{"CinGen ID":"CA229732","Variant Name":"NM_000277.2:c.739G>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":16256386,"Raw Comment":"Patient genotype: G247R+R413P (VarID 592, Pathogenic)","Number of Patients":1,"In trans Variants":["p.R413P c.(1238G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229700","Variant Name":"NM_000277.2:c.704A>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":16256386,"Raw Comment":"Q235P seen with IVS4-1G>A (VarID 594, pathogenic) in 1 patient.","Number of Patients":1,"In trans Variants":["IVS4-1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229391","Variant Name":"NM_000277.3:c.1199G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":16256386,"Raw Comment":"Seen in 3 individuals with classic PKU (PHE > 1200 umol\/L), in trans with IVS7+2T>A, R243Q (pathogenic), and G346R (pathogenic)","Number of Patients":3,"In trans Variants":["p.R243Q c.(728G>A)","p.G346R c.(1036G>C)","IVS7+2T>A"],"labels":"fine-tune"},{"CinGen ID":"CA229740","Variant Name":"NM_000277.2:c.746T>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":16256386,"Raw Comment":"Patient Genotype R243Q (VarID 591, Pathogenic) + L249H","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229266","Variant Name":"NM_000277.3:c.1007A>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":16256386,"Raw Comment":"Detected with R243Q, parental analysis not reported PMID: 16256386","Number of Patients":0,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229430","Variant Name":"NM_000277.3:c.1315+4A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":16256386,"Raw Comment":"This variant was documented in 1 Northern Chinese patient diagnosed with Classical PKU (Phe \u00e2\u0089\u00a5 1200 \u00c2\u00b5mol\/L) through neonatal screening. The variant in trans was the likely pathogenic R241fsX5 (c.722delG) variant. This study included 185 unrelated Northern Chinese PKU patients. It was not specified whether parental analysis was performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":"[\"R241fsX5 c.722delG\"]","labels":"fine-tune"},{"CinGen ID":"CA229427","Variant Name":"NM_000277.2:c.1301C>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":16256386,"Raw Comment":"A434D+Y356X (VarID 595, Pathogenic\/Likely Pathogenic) in 1 mild PKU patient. R252Q (VARID 102824, Pathogenic) + A434D in 1 classical PKU patient. R243Q (VarID 591, Pathogenic) + A434D in 1 classical PKU patient. Maternal or paternal inheritance of mutations was determined particularly for patients with novel mutation when parental DNA was available. Family gene analysis accomplished for each of them has also confirmed that the allele was inherited from the parent who did not carry other PKU mutations.","Number of Patients":3,"In trans Variants":["p.Y356X","p.R243Q c.(728G>A)","p.R252Q c.(755G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229771","Variant Name":"NM_000277.2:c.801G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":16256386,"Raw Comment":"Patient genotype: R252Q (VarID 102824, Pathogenic)+ Q267H. Maternal or paternal inheritance of mutations was determined particularly for patients with novel mutation when parental DNA was available.","Number of Patients":1,"In trans Variants":["p.R252Q c.(755G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229840","Variant Name":"NM_000277.2(PAH):c.904delT (p.Ser303Profs)","Condition":"phenylketonuria","Criterion":"PM3","PMID":16256386,"Raw Comment":"Observed with S70del (Table 2). Maternal or paternal inheritance of mutations was determined particularly for patients with novel mutation when parental DNA was available.","Number of Patients":"NA","In trans Variants":["S70del"],"labels":"fine-tune"},{"CinGen ID":"CA10575471","Variant Name":"NM_000419.5:c.409-2_419del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":16359514,"Raw Comment":"Eight patients from PMID: 16359514 meet the maximum of 1pt for homozygous occurrences. ","Number of Patients":8,"In trans Variants":["homozygous c.409-2_419del "],"labels":"fine-tune"},{"CinGen ID":"CA915940728","Variant Name":"NM_000212.3:c.153del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT07 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.153del p.(Trp51Cysfs*16)"],"labels":"fine-tune"},{"CinGen ID":"CA915940725","Variant Name":"NM_000419.5:c.2898_2902dup","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT24 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2898_2902dup p.(Tyr968Serfs*?)"],"labels":"fine-tune"},{"CinGen ID":"CA8622881","Variant Name":"NM_000212.3:c.166-14C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT03 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.166-14C>A "],"labels":"fine-tune"},{"CinGen ID":"CA400023445","Variant Name":"NM_000212.3:c.652C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT17 in PMID: 16463284), sufficient to apply PM3_Supporting. ","Number of Patients":1,"In trans Variants":["homozygous c.652C>T p.(His218Tyr)"],"labels":"fine-tune"},{"CinGen ID":"CA915940727","Variant Name":"NM_000419.5:c.727del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT41 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.727del p.(Leu243Phefs*136)"],"labels":"fine-tune"},{"CinGen ID":"CA400025209","Variant Name":"NM_000212.3:c.921C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in three individuals (GT21, GT25, and GT55 in PMID: 16463284), sufficient to apply PM3.","Number of Patients":3,"In trans Variants":["homozygous c.921C>A p.(Tyr307*)"],"labels":"fine-tune"},{"CinGen ID":"CA399802643","Variant Name":"NM_000419.5:c.1520C>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT43 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1520C>G p.(Pro507Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA399804402","Variant Name":"NM_000419.5:c.1139G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT28 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1139G>T p.(Gly380Val)"],"labels":"fine-tune"},{"CinGen ID":"CA915940722","Variant Name":"NM_000419.5:c.2459del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT02 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2459del p.(Asn820Metfs*6)"],"labels":"fine-tune"},{"CinGen ID":"CA915940723","Variant Name":"NM_000419.5:c.245dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT06 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.245dup p.(Gly83Argfs*20)"],"labels":"fine-tune"},{"CinGen ID":"CA399790170","Variant Name":"NM_000419.5:c.2953C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT38 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2953C>T p.(Gln985*)"],"labels":"fine-tune"},{"CinGen ID":"CA915940724","Variant Name":"NM_000419.5:c.2015del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT12 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2015del p.(Gly672Alafs*23)"],"labels":"fine-tune"},{"CinGen ID":"CA400029121","Variant Name":"NM_000212.3:c.1402G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT34 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1402G>T p.(Glu468*)"],"labels":"fine-tune"},{"CinGen ID":"CA399805152","Variant Name":"NM_000419.5:c.800-2A>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant was reported in homozygosity in one individual (GT27 in PMID: 16463284), sufficient to apply PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.800-2A>G "],"labels":"fine-tune"},{"CinGen ID":"CA400031666","Variant Name":"NM_000212.2:c.115T>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"Individual GT11 was predicted to be homozygous based on haplotype analysis and consanguinity status.","Number of Patients":1,"In trans Variants":["homozygous c.115T>G p.(Cys39Gly)"],"labels":"fine-tune"},{"CinGen ID":"CA915940958","Variant Name":"NM_000212.3:c.2187_2203delinsTCATTGGCTCA","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16463284,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia (PMID: 16463284). This individual was homozygous for the variant (0.5 points, PM3_Supporting). \n","Number of Patients":1,"In trans Variants":["homozygous c.2187_2203delinsTCATTGGCTCA p.(Ile730_Leu735delinsHisTrpLeuIle)"],"labels":"fine-tune"},{"CinGen ID":"CA132727","Variant Name":"NM_000441.1:c.349C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":16570074,"Raw Comment":"109 patients from 100 families with nonsyndromic hearing loss and EVA. 50 control individuals, study in France. The variant was seen in one affected patient without a second variant.","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":16570074,"Raw Comment":"This study identified a French patient with EVA and Mondini malformation with a homozygous p.V138F genotype.","Number of Patients":1,"In trans Variants":["homozygous c.412G>T p.(Val138Phe)"],"labels":"fine-tune"},{"CinGen ID":"CA229633","Variant Name":"NM_000277.2:c.581T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":16601866,"Raw Comment":"Patient 28 genotype: L194P\/R261X (VarID610, Path). All the mutations identified were confirmed by analysing parental DNA, which also enabled us to follow the segregation of the mutations.","Number of Patients":1,"In trans Variants":["p.R261X"],"labels":"fine-tune"},{"CinGen ID":"CA229269","Variant Name":"NM_000277.2:c.1012G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":16601866,"Raw Comment":"D338Y seen in trans with P281L (VarID 589, Pathogenic in ClinVar) in 1 patient with mild PKU. All the mutations identified were confirmed by analysing parental DNA.","Number of Patients":1,"In trans Variants":["p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229610","Variant Name":"NM_000277.3:c.529G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":16879198,"Raw Comment":"L48S+V177L. parental testing not reported.","Number of Patients":"NA","In trans Variants":["p.L48S c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA399804787","Variant Name":"NM_000419.5:c.953C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16879215,"Raw Comment":"UPN 3 is homozygous for this variant (PM3_supporting; PMID: 16879215).","Number of Patients":1,"In trans Variants":["homozygous c.953C>T p.(Ser318Leu)"],"labels":"fine-tune"},{"CinGen ID":"CA8603454","Variant Name":"NM_000419.5:c.475G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16879215,"Raw Comment":"UPN 2 (PMID: 16879215) is homozygous for this variant (PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.475G>A p.(Gly159Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA915940806","Variant Name":"NM_000212.3:c.330_336del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16879215,"Raw Comment":"UPN 10 is homozygous for this variant (PM3_supporting; PMID: 16879215).","Number of Patients":1,"In trans Variants":["homozygous c.330_336del p.(Ser110Argfs*32)"],"labels":"fine-tune"},{"CinGen ID":"CA8603212","Variant Name":"NM_000419.5:c.1162G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16879215,"Raw Comment":"UPN 4 is homozygous for this variant (PM3_supporting; PMID: 16879215).","Number of Patients":1,"In trans Variants":["homozygous c.1162G>A p.(Gly388Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA400032570","Variant Name":"NM_000212.3:c.1801T>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16879215,"Raw Comment":"1 homozygous proband from PMID: 16879215 meets criteria for PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1801T>G p.(Cys601Gly)"],"labels":"fine-tune"},{"CinGen ID":"CA8603039","Variant Name":"NM_000419.5:c.1545-1G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16879215,"Raw Comment":"UPN 5 is homozygous for this variant (PM3_supporting; PMID: 16879215).","Number of Patients":1,"In trans Variants":["homozygous c.1545-1G>A "],"labels":"fine-tune"},{"CinGen ID":"CA8602667","Variant Name":"NM_000419.5:c.2489T>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16879215,"Raw Comment":"UPN 9 is homozygous for this variant (PM3_supporting; PMID: 16879215).","Number of Patients":1,"In trans Variants":["homozygous c.2489T>G p.(Leu830Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA399807046","Variant Name":"NM_000419.5:c.48G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":16879215,"Raw Comment":"UPN 1 is homozygous for this variant (PM3_supporting; PMID: 16879215).","Number of Patients":1,"In trans Variants":["homozygous c.48G>A p.(Trp16*)"],"labels":"fine-tune"},{"CinGen ID":"CA294895065","Variant Name":"NM_000152.5:c.1626C>G","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":16917947,"Raw Comment":"This variant has been detected in the homozygous state in one individual with Pompe disease (0.5 pt, PMID 16917947) (PM3_Supporting).\n","Number of Patients":1,"In trans Variants":["homozygous c.1626C>G "],"labels":"fine-tune"},{"CinGen ID":"CA8815664","Variant Name":"NM_000152.4:c.2237G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Very Strong","PMID":16917947,"Raw Comment":"Seven patients are compound heterozygous for c.2237G>A (p.Trp746Ter) and c.-32-13T>G, a well-known pathogenic variant. The variants are confirmed to be in trans. Five out of the seven patients meet PP4 criteria. 5 points were awarded.","Number of Patients":7,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA274250","Variant Name":"NM_000152.3:c.2608C>T","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":17056254,"Raw Comment":"Patient 9 is compound heterozygous for c.2608C>T (p.Arg870Ter) and c.-32-13T>G (Pathogenic variant). The phase of the variants is unknown. GAA activity in lymphocytes is provided but the patient does not meet PP4, and therefore this data will not be included.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA8815664","Variant Name":"NM_000152.4:c.2237G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Very Strong","PMID":17056254,"Raw Comment":"Patient 13 is compound heterozygous for c.2237G>A (p.Trp746Ter) and c.-32-13T>G, a well-known pathogenic variant. The phase of the variants was not confirmed. This patient meets PP4 criteria. No points were awarded since the phase was not confirmed and in trans data for c.-32-13T>G has already been counted.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA400023428","Variant Name":"NM_000212.3:c.646T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":17083650,"Raw Comment":"This variant was detected in a homozygous state in a patient with GT type II (UPN 12; PMID 17083650).","Number of Patients":1,"In trans Variants":["homozygous c.646T>C p.(Tyr216His)"],"labels":"fine-tune"},{"CinGen ID":"CA254380","Variant Name":"NM_000156.6:c.148A>C","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":17101918,"Raw Comment":"PMID: 17101918: Reported in the homozygous state in one patient with guanidinoacetate methyltransferase deficiency (0.5pts)","Number of Patients":1,"In trans Variants":["homozygous c.148A>C p.(Met50Leu)"],"labels":"fine-tune"},{"CinGen ID":"CA409120239","Variant Name":"NM_000022.4:c.736C>T","Condition":"adenosine deaminase deficiency","Criterion":"PM3-Supporting","PMID":17185467,"Raw Comment":"One patient (U444) was found homozygous for this mutation (PMID: 17185467,PM3_Supporting)","Number of Patients":1,"In trans Variants":["homozygous c.736C>T p.(Gln246*)"],"labels":"fine-tune"},{"CinGen ID":"CA288488","Variant Name":"NM_024675.4:c.3549C>A","Condition":"hereditary breast cancer","Criterion":"PM3-Strong","PMID":17200671,"Raw Comment":"This variant, or another variant leading to the same protein truncation, has been detected in three individuals with Fanconi Anemia subtype FA-N. Of those individuals, three were compound heterozygous for the variant and a pathogenic or likely pathogenic variant and three of those were confirmed in trans by parental testing (co-occurring variants: c.2257C>T (p.Arg753Ter); c.2962C>T (p.Gln988Ter); c.3116delA (p.Asn1039Ilefs*2): PMID 17200671). (PM3_Strong).","Number of Patients":3,"In trans Variants":["c.2257C>T p.Arg753Ter","c.2962C>T p.Gln988Ter","c.3116delA p.Asn1039Ilefs\\*2"],"labels":"fine-tune"},{"CinGen ID":"CA269618","Variant Name":"NM_024675.3:c.3350+4A>G","Condition":"hereditary breast cancer","Criterion":"PM3","PMID":17200671,"Raw Comment":"This variant has been detected in two individuals with Fanconi Anemia. One individual was compound heterozygous for the variant and a pathogenic variant confirmed in trans by parental testing (PALB2 c.2393_2394insCT (p.Thr799fs), 2 points, PMID: 17200671). One individual was homozygous for the variant (0 points (not scored due to lack of confirmatory phenotypic and chromosome breakage test information, Invitae) (PM3).","Number of Patients":2,"In trans Variants":["c.2393_2394insCT p.Thr799fs","homozygous c.3350+4A>G"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":17309986,"Raw Comment":"Identified a case with EVA and a compound het genotype: G209V\/T410M. The G209V variant is a pathogenic variant in ClinVar by 5 submitters. This would count as 1.0 points for PM3","Number of Patients":1,"In trans Variants":["p.G209V c.(626G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA399795907","Variant Name":"NM_000419.5:c.2437C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":17488698,"Raw Comment":"The patient reported in PMID: 17488698 is compound heterozygous for c.1771dup and His813Asn. Variants are confirmed in trans by independent segregation in patient's daughters. (1pt; PM3)","Number of Patients":1,"In trans Variants":["c.1771dup p.(Asp591Glyfs*47)"],"labels":"fine-tune"},{"CinGen ID":"CA6748984","Variant Name":"NM_000277.2:c.307G>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":17502162,"Raw Comment":"Table 5. Sample 37. allele 1: c.1066-11G>A\/ allele 2; c.307G>T.","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16020722","Variant Name":"NM_000277.1:c.60+4A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":17502162,"Raw Comment":"Table 5: Variant observed in two compound heterozygote PKU patients, both in trans with a ClinVar pathogenic variant (c.1066-11G>A; c.842C>T Var 589).","Number of Patients":2,"In trans Variants":["c.842C>T p.(Pro281Leu)","c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA253314","Variant Name":"NM_000441.1:c.-103T>C","Condition":"Pendred syndrome","Criterion":"PM3","PMID":17503324,"Raw Comment":"Studied 429 patients with Pendred syndrome or nonsyndromic EVA. The -103T>C variant was observed in 9 patients. A second SLC26A4 variant was not identified in these families.","Number of Patients":9,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":17503324,"Raw Comment":"This study identified 6 patients with the p.V138F varaint who had PS-EVA, and they found that 4 of them had a second mutation identified however they don't describe what the other mutations were.","Number of Patients":4,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229813","Variant Name":"NM_000277.3:c.842+2T>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":17557229,"Raw Comment":"Detected in trans with: \nR111X (P, ClinGen)\nP281L (P, ClinGen)\nR413P (P, ClinGen)\nR243Q (P, ClinGen)\nR261Q (LP\/P, ClinGen)\nR400T (unknown, ClinGen)","Number of Patients":1,"In trans Variants":["p.P281L c.(842C>T)","p.R243Q c.(728G>A)","p.R111X","p.R413P c.(1238G>C)","p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA387460893","Variant Name":"NM_004004.6:c.563A>G","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Strong","PMID":17666888,"Raw Comment":"2.5 points from 3 probands\n1 proband reported in PMID 17666888\n1 proband internal data from University of Minnesota internal data, p.Lys188Arg \/ p.Leu90Pro, trans phasing inferred from NGS data\n1 proband internal data from GeneDx, p.Lys188Arg \/ c.35delG confirmed in trans","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA172208","Variant Name":"NM_004004.5:c.107T>C","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":17666888,"Raw Comment":"The p.L36P variant was found in two North American individuals with unspecified hearing loss. No variant was identified in trans","Number of Patients":2,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA172217","Variant Name":"NM_004004.5:c.167del","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":17666888,"Raw Comment":"carrier rate of 4% in AJ, variant representing 3.6% of GJB2 allelic variants, described in 1 double het with GJB6, reporting variant in 83 alleles (AR) up to 24% white and 7.2% AJ and 2.4 other (ethnic distribution),","Number of Patients":"NA","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA274250","Variant Name":"NM_000152.3:c.2608C>T","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":17723315,"Raw Comment":"Patient 23 (Table 1) is compound heterozygous for c.2608C>T (p.Arg870Ter) and c.-32-13T>G (Pathogenic variant). The phase of the variants is unknown. GAA activity in cultured fibroblasts is 13.2% normal, meeting PP4. 0.5 points.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA253338","Variant Name":"NM_022124.5:c.719C>T","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Strong","PMID":17850630,"Raw Comment":"Probands overlap with Miyagawa 2013. Four families with rare VUS in trans. Scored 1 point total.","Number of Patients":4,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA251528","Variant Name":"NM_000277.1:c.782G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":17935162,"Raw Comment":"The BIOPKUdb comprises genotypes information from 315 BH4-responsive patients. Patient genotypes mentioned: p.R261Q\/ p.L48S, p.R261Q\/p.R53H (VarID 102601, VUS\/LB); p.R261Q\/ p.S349P (VarID 615 P\/LP), p.R261Q\/p.R243X (VarID 588, P).","Number of Patients":4,"In trans Variants":["p.S349P c.(1045T>C)","p.L48S c.(143T>C)","p.R53H c.(158G>A)","p.R243X"],"labels":"fine-tune"},{"CinGen ID":"CA114362","Variant Name":"NM_000277.1:c.1241A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":17935162,"Raw Comment":"compound het patients","Number of Patients":"NA","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA397723695","Variant Name":"NM_000018.4:c.790A>G","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Supporting","PMID":17999356,"Raw Comment":"This variant has been detected in at least one individual with very long chain acyl CoA dehydrogenase\n(VLCAD) deficiency and a distinct pathogenic variant, though the variant was not confirmed to be in trans (PMID: 17999356; PM3_Supporting). ","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA278720","Variant Name":"NM_000260.4:c.977T>A","Condition":"Usher syndrome","Criterion":"PM3","PMID":18181211,"Raw Comment":"1.5 pts (18181211, LMM)","Number of Patients":"NA","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA180669","Variant Name":"NM_000260.4:c.2476G>A","Condition":"Usher syndrome","Criterion":"PM3","PMID":18181211,"Raw Comment":"557 Pakistani families with hearing loss were tested for variants in MYO7A. The p.Ala826Thr variant was identified in the homozygous state in one family. No segregation information was provided.","Number of Patients":1,"In trans Variants":["homozygous c.2476G>A p.(Ala826Thr)"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":18285825,"Raw Comment":"This study found 2 probands. One was heterozygous for the V138F variant who had LE Cophosis RE normal hearing. And the other patient and sibling had the V138F variant in trans with the p.Q514 variant.","Number of Patients":1,"In trans Variants":["p.Q514"],"labels":"fine-tune"},{"CinGen ID":"CA229452","Variant Name":"NM_000277.2:c.168+1G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":18294361,"Raw Comment":"homozygous in a single patient","Number of Patients":1,"In trans Variants":["homozygous c.168+1G>A "],"labels":"fine-tune"},{"CinGen ID":"CA273110","Variant Name":"NM_000277.2:c.533A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":18294361,"Raw Comment":"Detected with R408W (VarID577, Path), P281L (VarID589, Path), R261Q (VarID582, P\/LP), L48S (VarID608, Path)","Number of Patients":"NA","In trans Variants":["p.L48S c.(143T>C)","p.R408W c.(1222C>T)","p.R261Q c.(782G>A)","p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020991","Variant Name":"NM_001354304.2:c.1306del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":18299955,"Raw Comment":"found in presumed trans with the IVS10-11G>A variant (Pathogenic per ClinGen PAH VCEP) (PMID: 18299955) (0.5 points total; PM3_Supporting).","Number of Patients":"1","In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16020720","Variant Name":"NM_000277.1:c.48dup","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":18299955,"Raw Comment":"This variant was detected in a patient with classic PKU phenotype, who carried a second PAH variant (p.L48S).","Number of Patients":1,"In trans Variants":["p.L48S c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229603","Variant Name":"NM_000277.1:c.520A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":18299955,"Raw Comment":"Single patient: IVS4+5G>T \/ I174V \u00e2\u0080\u0093 mild PKU (plasma phe 6.5-10mg\/dl and tolerate 400-600mg\/day of dietary Phe)\u00e2\u0080\u0094no specific level listed","Number of Patients":1,"In trans Variants":["IVS4+5G>T"],"labels":"fine-tune"},{"CinGen ID":"CA229461","Variant Name":"NM_000277.2:c.169_171del","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":18299955,"Raw Comment":"A mild PKU patient is reported to be heterozygous for this variant and Ala403Val (ClinVar 92731, Pathogenic). This c.169_171del variant is referred to as \"IVS2 - 2 del\" in this article but this is in fact the intended variant as this paper is the reference provided in BIOPKU and HGMD has confirmed, by personal communication with the authors, that this is the c.169_171del variant.","Number of Patients":1,"In trans Variants":["p.Ala403Val c.(1208C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA267662","Variant Name":"NM_000277.2:c.591G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":18299955,"Raw Comment":"IVS2+1G>A (P by PAH WG) in 1 patient, homozygous in 2 patients. To identify homozygous mutations, 10 ll PCR product of wild-type DNA and 10 ll PCR product of sample DNA were mixed 1.1 and denatured at 95\u00c2\u00b0C. This enabled detection of homozygous mutations by formation of a heteroduplex.","Number of Patients":"err","In trans Variants":["IVS2+1G>A","homozygous c.591G>C p.(Leu197Phe)"],"labels":"fine-tune"},{"CinGen ID":"CA16020865","Variant Name":"NM_000277.1:c.813T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":18299955,"Raw Comment":"Patient genotype: IVS10-11G>A\/H271Q","Number of Patients":1,"In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16020840","Variant Name":"NM_000277.1:c.689T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":18299955,"Raw Comment":"V230A found in trans with V230I (Var ID 102784, Pathogenic\/LP) in 1 patient with MHP, and in trans with A300S (Var ID 92751, Pathogenic) in 1 patient with mild PKU.","Number of Patients":2,"In trans Variants":["p.V230I c.(688G>A)","p.A300S c.(898G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA891862634","Variant Name":"NM_000277.1:c.47_48insCT","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":18299955,"Raw Comment":"The variant has been previously reported in trans with the known pathogenic L48S allele in 1 Israeli case with classic PKU (PMID: 18299955; PMID: 18294361) as assessed by plasma Phe levels; BH4 deficiency was excluded.","Number of Patients":1,"In trans Variants":["p.L48S c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA251529","Variant Name":"NM_000277.1:c.754C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":18299955,"Raw Comment":"Patient genotype: IVS10-11G>A (VarID 607, Pathogenic) + R252W","Number of Patients":1,"In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA114365","Variant Name":"NM_000277.1:c.916A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":18299955,"Raw Comment":"Study in Israel. 200 PKU patients. Single patient with c.916A>G variant.","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA114364","Variant Name":"NM_000277.1:c.1243G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":18299955,"Raw Comment":"Patient genotype: IVS10 - 11G>A (VarID607, Pathogenic) + D415N","Number of Patients":1,"In trans Variants":["IVS10 - 11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16020788","Variant Name":"NM_001354304.2:c.441+5G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":18321666,"Raw Comment":"NL patient 3 of PMID: 18321666 is compound heterozygous for c.441+5G>A and R158Q (ClinVar 587, Pathogenic reviewed by VCEP). Confirmation of phase not reported.","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA16020834","Variant Name":"NM_000277.1:c.667A>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":18346471,"Raw Comment":"PMID 18346471: Table 1 listed c.165delT\/p.N223Y in one patient with Phe 242uM","Number of Patients":1,"In trans Variants":["c.165delT p.(Phe55Leufs*6)"],"labels":"fine-tune"},{"CinGen ID":"CA16020737","Variant Name":"NM_000277.3:c.184del","Condition":"phenylketonuria","Criterion":"PM3","PMID":18346471,"Raw Comment":"Detected in trans with the known pathogenic p.A403V allele in an Italian proband (PMID: 18346471).","Number of Patients":1,"In trans Variants":["p.A403V c.(1208C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA8815664","Variant Name":"NM_000152.4:c.2237G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Very Strong","PMID":18429042,"Raw Comment":"Patient 4 is compound heterozygous for c.2237G>A (p.Trp746Ter) and c.525delT (p.Glu176fsX45) and patient 11 is compound heterozygous for c.2237G>A and c.1655T>C (p.Leu552Pro). These patients do not meet PP4 criteria and therefore no points were awarded.","Number of Patients":2,"In trans Variants":["c.525delT p.Glu176fsX45","c.1655T>C p.Leu552Pro"],"labels":"fine-tune"},{"CinGen ID":"CA273892","Variant Name":"NM_000152.3:c.1933G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":18429042,"Raw Comment":"Patient 21 is compound heterozygous for c.1933G>A (p.Asp645Asn) and c.1564C>G (p.P522A). The phase of the variants is unknown. The diagnosis was based on clinical data and confirmed by reduced lysosomal \u00ce\u00b1-glucosidase activity in different tissues (fibroblasts and\/or blood samples). However, individual GAA activity is not available and therefore this data will not be included.","Number of Patients":1,"In trans Variants":["c.1564C>G p.P522A"],"labels":"fine-tune"},{"CinGen ID":"CA274311","Variant Name":"NM_000152.4:c.1128_1129delGGinsC","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":18607768,"Raw Comment":"c.1128_1129delGGinsC was found in compound heterozygosity with c.885C>G (p.His295Gln), a variant of unknown significance, in an individual with late onset Pompe disease and GAA activity <30% of lower normal range in muscle. The phase of the variants is unknown. No points are given because the second variant is a variant of unknown significance and the patient does not meet PP4 criteria.","Number of Patients":1,"In trans Variants":["c.885C>G p.His295Gln"],"labels":"fine-tune"},{"CinGen ID":"CA252228","Variant Name":"NM_007123.5:c.4338_4339delCT","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":18641288,"Raw Comment":"This study identified 3 USH2 patients with the Cys1447fs variant that also had the Cys759Phe variant which has been classified by several labs in ClinVar (including LMM who cite 14 publications) as Pathogenic.","Number of Patients":3,"In trans Variants":["p.Cys759Phe c.(2276G>T)"],"labels":"eval"},{"CinGen ID":"CA262109","Variant Name":"NM_206933.3:c.5857+2T>C","Condition":"Usher syndrome","Criterion":"PM3","PMID":18641288,"Raw Comment":"1 patient with Usher syndrome, who was compound het with the pathogenic Cys759Phe, though it was not clear if phasing was performed.","Number of Patients":1,"In trans Variants":["p.Cys759Phe c.(2276G>T)"],"labels":"eval"},{"CinGen ID":"CA252228","Variant Name":"NM_007123.5:c.4338_4339delCT","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":18665195,"Raw Comment":"Used genotyping assays to identify the c.4338_4339delCT variant in 4\/9 homozygous probands from Canada. Observed no carriers of the variant in 207 healthy controls from Quebec. Additionally, there was one French Canadian patient from Quebec who was compound heterozygous for the c.4338_4339delCT and c.2299delG variants with Usher syndrome.","Number of Patients":5,"In trans Variants":["c.2299delG p.(Glu767Serfs*21)"],"labels":"fine-tune"},{"CinGen ID":"CA10585257","Variant Name":"NM_000527.5:c.1027G>T","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":18757057,"Raw Comment":"Variant meets PM2 and is identified in an index case with homozygous FH phenotype with plasma LDL-C 16.62 mmol\/L, reported by Jelassi et al, PMID 18757057. This variant met enough pathogenic criteria toward Pathogenic classification by these guidelines before PM3 code applied.","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA400023604","Variant Name":"NM_000212.3:c.728A>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":18832906,"Raw Comment":"This variant has been observed in homozygosity in one proband (PMID: 18832906), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.728A>T p.(Asp243Val)"],"labels":"fine-tune"},{"CinGen ID":"CA229559","Variant Name":"NM_000277.2:c.464G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":18937047,"Raw Comment":"Patients 15-18 (siblings) had genotype p.D143G\/p.R155H","Number of Patients":4,"In trans Variants":["p.D143G c.(428A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA172240","Variant Name":"NM_004004.5:c.71G>A","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":18941476,"Raw Comment":"530 individuals with nonzyndromic hearing loss from India sequenced. 74 individuals were homozygous for the W24* variant, 9 individuals were heterozygous for the variant, and 17 individuals were compound heterozygous for the variant. The second variant was not specified.","Number of Patients":100,"In trans Variants":"[\"homozygous\"]","labels":"fine-tune"},{"CinGen ID":"CA229622","Variant Name":"NM_000277.2:c.559T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":18956252,"Raw Comment":"found in 1 case, in trans with p.R158Q allele (established pathogenic allele). Patient was German male diagnosed at 5d old with classic PKU based on plasma Phe, BH4 deficiency does not appear to have been excluded (see https:\/\/agbi.techfak.uni-bielefeld.de\/ramedis\/htdocs\/dm-guest\/case_main.php?patID=533).","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA399805912","Variant Name":"NM_000419.5:c.470C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":18976939,"Raw Comment":"This variant has been detected in at least 1 probands with Glanzmann thrombasthenia. This\nindividuals was homozygous for the variant (PMID: 18976939, 0.5 PM3 points)\nTotal points: 0.5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.470C>A p.(Pro157His)"],"labels":"fine-tune"},{"CinGen ID":"CA229732","Variant Name":"NM_000277.2:c.739G>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":18985011,"Raw Comment":"Patient genotype: p.Gly247Arg\/p.Val388Met (VarID 619, Pathogenic). Blood samples were collected from the patients and their family members.","Number of Patients":1,"In trans Variants":["p.Val388Met c.(1162G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229885","Variant Name":"NM_000277.3:c.975C>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":18985011,"Raw Comment":"two patients with this variant, both patients in trans with a second pathogenic variant.","Number of Patients":"2","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229548","Variant Name":"NM_000277.2:c.441+4A>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":19015950,"Raw Comment":"In the EQA scheme, three DNA samples with previously characterized genotypes were sent to each participant along with mock clinical descriptions. 2005, Patient 2, Comp. het.: IVS4+4A>G (c.441+4G>A) and p.Val230Ile (c.688G>A). Parental confirmation not reported.","Number of Patients":1,"In trans Variants":["p.Val230Ile c.688G>A"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":19017801,"Raw Comment":"This study identified another indiviudal with the p.T410M\/p.D724G genotype. This individual had severe\/profound hearing loss, Mondini malformation. This individual was actually a proband for family S154 which had 4 other individuals who were homozygous for the p.T410M varaint and had profound HL and EVA.","Number of Patients":5,"In trans Variants":["p.T410M c.(1229C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA262122","Variant Name":"NM_206933.2:c.8559-2A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":19023448,"Raw Comment":"2 Usher affected families:\n\nF4: 2 individuals having a p.R34fs frameshift variant in trans with the splice variant. There were 4 unaffected sibs (2 het for p.R34fs, 2 WT\/WT).\n\nF3: Variant was inherited in trans with a p.T3936P variant in USH2A in other family. This individual has an unaffected sib with only the p.T3936P variant and experienced HL onset at age 10 while other individuals had congenital HL.","Number of Patients":4,"In trans Variants":["p.R34fs c.99_100insT","p.T3936P c.(11806A>C)"],"labels":"eval"},{"CinGen ID":"CA023690","Variant Name":"NM_000527.5:c.313+2T>C","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":19026292,"Raw Comment":"Variant meets PM2 and is identified in a true homozygous with total cholesterol = 658 mg\/dl (PMID: 19026292), so PM3 is Met.","Number of Patients":1,"In trans Variants":["homozygous c.313+2T>C "],"labels":"fine-tune"},{"CinGen ID":"CA2499307108","Variant Name":"NM_000156.6:c.610_611delinsGAA","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":19027335,"Raw Comment":"PMID: 19027335: patient comp het for c.402C > G (p.Y134X) (path, ClinVar ID 947458) \/c.610_611delAGinsGAA (p.R204EfsX63), phase not confirmed. (0.5pts)","Number of Patients":1,"In trans Variants":["c.402C>G p.Y134X"],"labels":"fine-tune"},{"CinGen ID":"CA402995388","Variant Name":"NM_138924.3:c.403G>T","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":19027335,"Raw Comment":"PMID: 19027335: Identified in one individual who was a reported compound heterozygote who carried a reported pathogenic variant (c.507_521dup15 (p.C169_S173dup), ClinVar Variation ID: 431959) in unknown phase (0.5pts) ","Number of Patients":1,"In trans Variants":[],"labels":"fine-tune"},{"CinGen ID":"CA399805008","Variant Name":"NM_000419.5:c.859G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19172520,"Raw Comment":"Patient 5 (PMID: 19172520\/GT database record 162) is homozygous for this variant (0.5pt; PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.859G>C p.(Gly287Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA8603502","Variant Name":"NM_000419.5:c.310+1G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19172520,"Raw Comment":"Patient 3 (PMID: 19172520\/GT database record 160) is homozygous for this variant (0.5pt; PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.310+1G>A "],"labels":"fine-tune"},{"CinGen ID":"CA915940796","Variant Name":"NM_000419.5:c.2415_2416del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19172520,"Raw Comment":"Patient 10 (PMID: 19172520\/GT database record 167) is homozygous for this variant (0.5pt; PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.2415_2416del p.(Asp805Glufs*11)"],"labels":"fine-tune"},{"CinGen ID":"CA399802454","Variant Name":"NM_000419.5:c.1600+1G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19172520,"Raw Comment":"This variant has been detected in the homozygous state in at least 2 probands with Glanzmann thrombasthenia. However, these two individuals are related (PMID: 19172520) and only one affected individual per family can be counted towards PM3. Total points: 0.5 (PM3_Supporting).\n","Number of Patients":2,"In trans Variants":["homozygous c.1600+1G>A "],"labels":"fine-tune"},{"CinGen ID":"CA399798192","Variant Name":"NM_000419.5:c.2255T>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":19175981,"Raw Comment":"An individual reported in PMID: 19175981 (and as Patient 180 in the Glanzmann Thrombasthenia Database, https:\/\/glanzmann.mcw.edu) is compound heterozygous (phase confirmed) for this variant and c.2671C>T (p.Gln891Ter, classified as pathogenic by the Platelet Disorders VCEP) (PM3).","Number of Patients":1,"In trans Variants":["c.2671C>T p.Gln891Ter"],"labels":"fine-tune"},{"CinGen ID":"CA261400","Variant Name":"NM_000441.2:c.1204G>A","Condition":"Pendred syndrome","Criterion":"PM3-Strong","PMID":19204907,"Raw Comment":"Found in a proband with enlarged vestibular aqueducts in compound heterozygosity with the p.L445W variant in CDH23. The p.L445W variant is absent from gnomAD v2.1.1 and v3 and functional evidence from this publication shows the allele-product is retained within the ER (PMID: 19204907).\n\nThis variant was also found in a proband with congenital mild to moderate sensorineural hearing loss with the 1437+2T>G splicing variant (P\/LP in ClinVar, Variation ID: 43508) confirmed in trans.","Number of Patients":1,"In trans Variants":["p.L445W c.(1334T>G)"],"labels":"eval"},{"CinGen ID":"CA253314","Variant Name":"NM_000441.1:c.-103T>C","Condition":"Pendred syndrome","Criterion":"PM3","PMID":19204907,"Raw Comment":"Studied 47 patients with EVA from 41 families. Identified the -103T>C variant in trans with p.L236P, in one white 8-month-old with bilateral EVA and an indeterminate thyroid phenotype. Did not identified the -103T>C variant in 146 ethnically matched (Caucasian) control or 106 ethnically diverse control chromosomes.","Number of Patients":1,"In trans Variants":["p.L236P c.(707T>C)"],"labels":"eval"},{"CinGen ID":"CA402996427","Variant Name":"NM_138924.3:c.274A>G","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":19288536,"Raw Comment":"Identified in one individual with guanidinoacetate methyltransferase deficiency, who was a homozygote for the variant (0.5pts) (PMID: 19288536)","Number of Patients":1,"In trans Variants":["homozygous c.274A>G p.(Asn92Asp)"],"labels":"fine-tune"},{"CinGen ID":"CA16020846","Variant Name":"NM_000277.3:c.707-2del","Condition":"phenylketonuria","Criterion":"PM3","PMID":19292873,"Raw Comment":"Seen in trans with pathogenic p.P281L.","Number of Patients":1,"In trans Variants":["p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA251535","Variant Name":"NM_000277.3:c.281_283TCA[1]","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":19292873,"Raw Comment":"Documented in 1 Southern Italian patient diagnosed with hyperphenylalaninemia (HPA), who was a compound heterozygote with the likely pathogenic c.165delT variant in trans. Parental analysis was not performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["c.165delT p.(Phe55Leufs*6)"],"labels":"fine-tune"},{"CinGen ID":"CA273109","Variant Name":"NM_000277.1:c.638T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":19292873,"Raw Comment":"L213P in trans with c.1066-11G>A ((Pathogenic in ClinVar, VarID 607)","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16020889","Variant Name":"NM_000277.3:c.902A>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":19292873,"Raw Comment":"Detected in trans with pathogenic p.L48S (table 2).","Number of Patients":1,"In trans Variants":["p.L48S c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":19509082,"Raw Comment":"This study identified 2 patients with the p.T410M variant and NSHL w\/a temporal bone abnormality. One individual was homozygous and the other had a c.1199insT variant (p.Cys400TrpfsX68) which is a convincing LOF variant. This paper would also provide 1.5 PM3 points.","Number of Patients":2,"In trans Variants":["homozygous c.1229C>T p.(Thr410Met)","c.1199insT p.Cys400TrpfsX68"],"labels":"fine-tune"},{"CinGen ID":"CA401369859","Variant Name":"NM_000152.5:c.1905C>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":19588081,"Raw Comment":"Two patients have been reported to be compound heterozygous for the variant and another variant in GAA that has been classified as pathogenic by the ClinGen LD VCEP, c.2501_2502delCA (p.Thr834Argfs48Ter) or c.-32-3C>A. The phase is not confirmed (2 x 0.5). A further two probands are homozygous for the variant (PMID: 19588081) (2 x 0.5). Total 2 points (PM3_Strong). ","Number of Patients":2,"In trans Variants":["homozygous c.1905C>A p.(Asn635Lys)"],"labels":"fine-tune"},{"CinGen ID":"CA10605404","Variant Name":"NM_000152.3:c.2501_2502delCA","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":19588081,"Raw Comment":"Patients 8, 11, and 14 are compound heterozygotes for c.2501_2502delCA and c.377G>A, c.2560C>T, and c.1905C>A, in GAA, respectively. However, the phase of the variants was not confirmed and the patients do not meet PP4 (0 points).","Number of Patients":3,"In trans Variants":["c.1905C>A p.(Asn635Lys)","c.377G>A p.(Trp126*)","c.2560C>T p.(Arg854*)"],"labels":"fine-tune"},{"CinGen ID":"CA274250","Variant Name":"NM_000152.3:c.2608C>T","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":19588081,"Raw Comment":"Patient 13 is homozygous for c.2608C>T (p.Arg870Ter). No parental testing or GAA activity results are available. Therefore, this data will not be included.","Number of Patients":1,"In trans Variants":["homozygous c.2608C>T p.(Arg870*)"],"labels":"fine-tune"},{"CinGen ID":"CA294887189","Variant Name":"NM_000152.5:c.377G>A","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":19588081,"Raw Comment":"This variant was found in patient 23 with c.1655T>C (p.Leu552Pro). c.1655T > C (p.Leu552Pro) is pathogenic based on assessment by the ClinGen LSD VCEP. This variant was also found in patient 8 with c.2501_2502delCA (p.Thr834Argfs48X). The phase of the variants was not confirmed and the patients do not meet PP4 criteria. Therefore, 0 points were awarded.","Number of Patients":2,"In trans Variants":["c.2501_2502delCA p.Thr834Argfs48X","c.1655T>C p.Leu552Pro"],"labels":"fine-tune"},{"CinGen ID":"CA229500","Variant Name":"NM_000277.2:c.250G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":19609714,"Raw Comment":"Patient genotype: [D84Y] + [R158Q] (VarID 587, pathogenic)","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229610","Variant Name":"NM_000277.3:c.529G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":19609714,"Raw Comment":"[V177L]+[F39del]. parental testing not reported.","Number of Patients":1,"In trans Variants":["p.F39del"],"labels":"fine-tune"},{"CinGen ID":"CA626379036","Variant Name":"NM_000212.3:c.887_901del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19691478,"Raw Comment":"This variant has been detected in at least 1 probands with Glanzmann thrombasthenia. One of those probands were homozygous for the variant (PM3: .5, PMID:19691478).","Number of Patients":1,"In trans Variants":["homozygous c.887_901del p.(Asp296_His300del)"],"labels":"fine-tune"},{"CinGen ID":"CA400034691","Variant Name":"NM_000212.3:c.2315T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19691478,"Raw Comment":"Patient GT3 reported in PMID: 19691478 is homozygous for this variant (PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.2315T>C p.(Leu772Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA115839","Variant Name":"NM_000419.4:c.1073G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":19691478,"Raw Comment":"Patient GT45 is homozygous for Arg358His. 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.1073G>A p.(Arg358His)"],"labels":"fine-tune"},{"CinGen ID":"CA400030171","Variant Name":"NM_000212.3:c.1641C>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19691478,"Raw Comment":"Patient GT72 reported in PMID: 19691478 is homozygous for this variant (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1641C>G p.(Cys547Trp)"],"labels":"fine-tune"},{"CinGen ID":"CA915940262","Variant Name":"NM_000419.4:c.3115_3119dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19691478,"Raw Comment":"Patient 51 is homozygous for this variant, as recorded in the GT database.","Number of Patients":1,"In trans Variants":["homozygous c.3115_3119dup p.(*1040Trpext*?)"],"labels":"fine-tune"},{"CinGen ID":"CA8603182","Variant Name":"NM_000419.4:c.1234G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Strong","PMID":19691478,"Raw Comment":"Patient GT37 is homozygous for Gly412Arg (the homozygous state of this patient is reported in PMID: 25275492). 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.1234G>A p.(Gly412Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA915940689","Variant Name":"NM_000212.3:c.674del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19691478,"Raw Comment":"This variant has been detected in at least one proband with Glanzmann thrombasthenia. The reported proband (GT30, PMID: 19691478) was homozygous for the variant (0.5 points). Total points: 0.5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.674del p.(Gln225Argfs*2)"],"labels":"fine-tune"},{"CinGen ID":"CA400031593","Variant Name":"NM_000212.3:c.92G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19691478,"Raw Comment":"Patient GT39 reported in PMID: 19691478 is homozygous for this variant (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.92G>A p.(Cys31Tyr)"],"labels":"fine-tune"},{"CinGen ID":"CA400028389","Variant Name":"NM_000212.3:c.59T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19691478,"Raw Comment":"Patient GT10 reported in PMID: 19691478 is homozygous for this variant (PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.59T>C p.(Leu20Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA115848","Variant Name":"NM_000419.4:c.641T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":19691478,"Raw Comment":"3 homozygous individuals, GT12, GT26 and GT68 meet criteria for PM3.","Number of Patients":3,"In trans Variants":["homozygous c.641T>C p.(Leu214Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA400025639","Variant Name":"NM_000212.2:c.953T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":19691478,"Raw Comment":"The Leu318Ser variant has been observed in one homozygous case (PMID: 19691478).","Number of Patients":1,"In trans Variants":["homozygous c.953T>C p.(Leu318Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA8602531","Variant Name":"NM_000419.4:c.2915dup","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":19691478,"Raw Comment":"Patient GT18 is compound heterozygous for the paternally inherited c.2915dup in trans with 2 maternally inherited variants Leu343Pro and g.951. Since VUS Leu343Pro is in cis with VUS g.951G>A this prband is not used for PM3.","Number of Patients":1,"In trans Variants":["p.Leu343Pro c.(1028T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA262122","Variant Name":"NM_206933.2:c.8559-2A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":19737284,"Raw Comment":"3 probands identified with Usher syndrome. 1 proband has variant in trans with Asp3515Gly (0.25 point), 1 proband has variant in trans with Thr3571Met (LP per LMM, 1 point), 1 proband has the variant in trans with a p.Trp3150X variant, however phase was not confirmed for this individual (0.5 points).","Number of Patients":3,"In trans Variants":["p.Trp3150X","p.Asp3515Gly c.(10544A>G)","p.Thr3571Met c.(10712C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA10605471","Variant Name":"NM_000152.4:c.1754+1G>A","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":19775921,"Raw Comment":"This variant was found in trans with a pathogenic variant in GAA in a patient with infantile-onset Pompe disease with <1% GAA activity in fibroblasts or muscle (PMID 19775921). Based on the ClinGen LSD VCEP's guidelines, this data was given a total of 1 point, meeting PM3.","Number of Patients":"err","In trans Variants":["c.722_723delTT p.(Phe241Cys fs-Ter 88)"],"labels":"eval"},{"CinGen ID":"CA658795235","Variant Name":"NM_000152.5:c.722_723del","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":19775921,"Raw Comment":"This variant has been found in at least two patients with Pompe disease who meet the ClinGen LSD VCEP\u00e2\u0080\u0099s specifications for PP4 (PMID 19775921). One of these patients is compound heterozygous for the variant and c.1687C>T (p.Gln563Ter), and the other is compound heterozygous for the variant and c.1754+1G>A. In both cases, the variants were confirmed to be in trans. One point was given to each case (total 2 points), meeting PM3_Strong.","Number of Patients":2,"In trans Variants":["c.1687C>T p.Gln563Ter","c.1754+1G>A"],"labels":"eval"},{"CinGen ID":"CA229522","Variant Name":"NM_000277.3:c.359G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":19786003,"Raw Comment":"1 patient was found to be homozygous for p.W125X (PMID:19786003). Parental and familial DNA was sequenced.","Number of Patients":1,"In trans Variants":["homozygous c.359G>A p.(Trp120*)"],"labels":"fine-tune"},{"CinGen ID":"CA16020822","Variant Name":"NM_001354304.2:c.586T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":19786003,"Raw Comment":"Observed in trans to c.1055del (p.Gly352fs) (Pathogenic according to PAH VCEP Variation ID: 102498) PMID: 19786003.","Number of Patients":1,"In trans Variants":"[\"c.1055del p.Gly352fs\"]","labels":"fine-tune"},{"CinGen ID":"CA229579","Variant Name":"NM_000277.2:c.493G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":19786003,"Raw Comment":"Patient 20: homozygous for p.A165T. Mendelian inheritance in parents and carrier analysis was performed by DGGE. Thus, it was possible to confirm homozygosity due to mutation inheritance from both parents and also to define the carriers.","Number of Patients":1,"In trans Variants":["homozygous c.493G>A p.(Ala165Thr)"],"labels":"fine-tune"},{"CinGen ID":"CA16020757","Variant Name":"NM_001354304.2:c.253A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":19786003,"Raw Comment":"3 patients were found to be homozygous for p.K85X (PMID: 19786003). Parental and familial DNA were sequenced.","Number of Patients":3,"In trans Variants":["homozygous c.253A>T p.(Lys85*)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":19786220,"Raw Comment":"Identified pT410M in trans with p.N392Y in a Chinese EVA patient. This variant has been identified as pathogenic by one submitter in ClinVar (Dividsion of Hearing and Balance Research, NHO Tokyo).","Number of Patients":1,"In trans Variants":["p.N392Y c.(1174A>T)"],"labels":"eval"},{"CinGen ID":"CA115850","Variant Name":"NM_000419.4:c.2870C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":20020534,"Raw Comment":"Patient 16 was homozygous for the Ser957Leu variant. 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.2870C>T p.(Ser957Leu)"],"labels":"fine-tune"},{"CinGen ID":"CA8602816","Variant Name":"NM_000419.4:c.2113T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":20020534,"Raw Comment":"Patient GT-12 is compound heterozygous for Cys705Arg and c.3060+2T>C (curated as Likely Pathogenic by the ClinGen Platelet Disorders VCEP; this Cys705Arg variant can be used in the assessment of c.3060+2T>C so will not be used here to avoid a circular argument). Confirmation of trans phase was not reported.","Number of Patients":"err","In trans Variants":["c.3060+2T>C"],"labels":"fine-tune"},{"CinGen ID":"CA290949843","Variant Name":"NM_000419.5:c.1672C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":20020534,"Raw Comment":"This variant was reported in homozygosity in one individual (CabGT-8 in PMID: 20020534). This homozygous occurrence earns 0.5 points and is sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1672C>T p.(Gln558*)"],"labels":"fine-tune"},{"CinGen ID":"CA290954352","Variant Name":"NM_000419.5:c.917dup","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":20020534,"Raw Comment":"This variant has been reported in heterozygosity in an individual harboring a second heterozygous ITGA2B variant (c.1913dup, p.Cys639MetfsTer22) provisionally classified as pathogenic by the Platelet Disorders VCEP without confirmation of phase (CabGT-2, PMID: 20020534). This co-occurrence earns 0.5 points, sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["c.1913dup p.Cys639MetfsTer22"],"labels":"fine-tune"},{"CinGen ID":"CA274311","Variant Name":"NM_000152.4:c.1128_1129delGGinsC","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":20033296,"Raw Comment":"p.Trp376Cysfs was found in compound heterozygosity with p.Gly219Arg. This data was not counted because the cDNA changes for the variants were not provided.","Number of Patients":1,"In trans Variants":["p.Gly219Arg c.(655G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA285294","Variant Name":"NM_000018.4:c.848T>C","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Strong","PMID":20107901,"Raw Comment":"This variant was identified in trans with a splice variant c.342+1G>C (paternally inherited and classified as likely pathogenic by VECP) in a neonate died at 38 hours of life with a postmortem C14:1 of 1.35 \u00ce\u00bcmol\/L (PMID 20107901). Homozygous in 2 patients. ","Number of Patients":3,"In trans Variants":["c.342+1G>C","homozygous c.848T>C p.(Val283Ala)"],"labels":"fine-tune"},{"CinGen ID":"CA229789","Variant Name":"NM_000277.2:c.823C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":20123475,"Raw Comment":"in trans with R408W","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA1139768925","Variant Name":"NM_001354304.2:c.1176dup","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":20188615,"Raw Comment":"The proband of Family 2 in PMID: 20188615 is homozygous for the c.1176dup (reported as c.1177insT). 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.1176dup p.(Asn393*)"],"labels":"fine-tune"},{"CinGen ID":"CA229811","Variant Name":"NM_000277.2:c.842+1G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":20188615,"Raw Comment":"Identified in homozygous state","Number of Patients":1,"In trans Variants":["homozygous c.842+1G>A "],"labels":"fine-tune"},{"CinGen ID":"CA387460990","Variant Name":"NM_004004.5:c.516G>C","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Supporting","PMID":20201936,"Raw Comment":"534 Mongolian individuals with hearing loss were tested for variants in GJB2. The p.Trp172Cys variant was identified in one individual who was compound het for the c.299_300delAT. It was absent from 217 controls.","Number of Patients":1,"In trans Variants":["c.299_300delAT p.(His100Argfs*14)"],"labels":"eval"},{"CinGen ID":"CA229719","Variant Name":"NM_000277.1:c.728G>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":20217238,"Raw Comment":"detected with p.R261Q (P 9 submitters) PMID: 20217238 parental analysis not reported","Number of Patients":1,"In trans Variants":["p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA252228","Variant Name":"NM_007123.5:c.4338_4339delCT","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":20440071,"Raw Comment":"This study identified another 2 French Canadian patients with the p.C1447QfsX variant who were homozygous for the variant but one also had a p.R56PfsX het. variant in PDZD7 which seemed to exacerbate the retinal phenotype.","Number of Patients":"err","In trans Variants":["homozygous p.(Cys1447Glnfs*29) c.4338_4339delCT","p.R56PfsX"],"labels":"fine-tune"},{"CinGen ID":"CA262109","Variant Name":"NM_206933.3:c.5857+2T>C","Condition":"Usher syndrome","Criterion":"PM3","PMID":20507924,"Raw Comment":"2 heterozygous patients with Usher syndrome, but unclear if they had a second variant in trans.","Number of Patients":2,"In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA400025615","Variant Name":"NM_000212.3:c.941A>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":20514620,"Raw Comment":"This variant has been reported in homozygous state in one proband. (PMID: 20514620) ) 0.5 points","Number of Patients":1,"In trans Variants":["homozygous c.941A>C p.(Asp314Ala)"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":20597900,"Raw Comment":"This study identified the p.Val138Phe variant in 6 patients with EVA and hearing loss. However, there were only 2 patietns with biallelic pathogenic SLC26A4 mutations. One patient had a c.1001+1G>A varaint and the other had the Leu445Trp variant. Of note, there were 4 affected heterozygotes.","Number of Patients":2,"In trans Variants":["p.Leu445Trp c.(1334T>G)","c.1001+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA274330","Variant Name":"NM_000152.5:c.365del","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":20638881,"Raw Comment":"One patient with Pompe disease is compound heterozygous for the variant and c.-32-13T>G (PMID: 20638881). The phase is not confirmed. 0.5 points were given, meeting PM3_Supporting.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA274024","Variant Name":"NM_000152.4:c.1051delG","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":20817528,"Raw Comment":"This variant was found in patient 2 with c.-32-13T>G. c.-32-13T>G is a well known pathogenic variant. The phase of the variants was not confirmed. This patient meets PP4 criteria. 0.5 points were awarded.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA915940386","Variant Name":"NM_000419.5:c.2930del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":20819594,"Raw Comment":"PMID: 20819594 Patient is compound heterozygous for the paternal c.1545-1del variant (classified by the Platelet Disorders VCEP as Pathogenic) and maternal c.2930del variant. 1pt","Number of Patients":1,"In trans Variants":["c.1545-1del"],"labels":"fine-tune"},{"CinGen ID":"CA399806951","Variant Name":"NM_000419.5:c.97A>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":21029361,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. One proband was homozygous for the variant (PMID:21029361). Total points: .5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.97A>G p.(Asn33Asp)"],"labels":"fine-tune"},{"CinGen ID":"CA387460667","Variant Name":"NM_004004.5:c.674C>T","Condition":"nonsyndromic genetic deafness","Criterion":"PM3","PMID":21112098,"Raw Comment":"p.Pro225Leu variant was found in trans with the common p.G45E\/p.Y136X allele common in the Japanese population in a proband with profound deafness. The p.G45E variant on its own causes lethal dominant KID syndrome but the nonsense variant \"protects\" from this more severe phenotype. Confirmed in trans","Number of Patients":1,"In trans Variants":["p.G45E c.(134G>A)","p.Y136X"],"labels":"fine-tune"},{"CinGen ID":"CA500261104","Variant Name":"NM_000419.5:c.3060G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":21113249,"Raw Comment":"Patient TA is homozygous for c.3060G>A, parents confirmed heterozygotes (PM3_supporting; PMID: 21113249)","Number of Patients":1,"In trans Variants":["homozygous c.3060G>A "],"labels":"fine-tune"},{"CinGen ID":"CA626684864","Variant Name":"NM_000212.2:c.1550del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":21113249,"Raw Comment":"Patient YF is homozygous for c.1550del .","Number of Patients":1,"In trans Variants":["homozygous c.1550del p.(Gly517Valfs*152)"],"labels":"fine-tune"},{"CinGen ID":"CA399787956","Variant Name":"NM_000419.5:c.3062T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":21113249,"Raw Comment":"Patient LN is homozygous for c.3062T>C 0.5pt (PM3_supporting; PMID: 21113249).","Number of Patients":1,"In trans Variants":["homozygous c.3062T>C p.(Val1021Ala)"],"labels":"fine-tune"},{"CinGen ID":"CA913012619","Variant Name":"NM_000212.3:c.2068_2069del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":21113249,"Raw Comment":"Patient PJ is homozygous for c.2068_2069del. 0.5pt\t(PM3_supporting; PMID: 21113249).","Number of Patients":1,"In trans Variants":["homozygous c.2068_2069del p.(Val690Argfs*7)"],"labels":"fine-tune"},{"CinGen ID":"CA399805570","Variant Name":"NM_000419.5:c.620C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":21113249,"Raw Comment":"One homozygous patient (OK) has been reported in PMID: 21113249. 0.5pt (PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.620C>T p.(Thr207Ile)"],"labels":"fine-tune"},{"CinGen ID":"CA400025098","Variant Name":"NM_000212.3:c.892C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":21136216,"Raw Comment":"PMID: 21136216 Patient is homozygous for Gln298Ter (reported as 892C>T Arg272Ter but sequence trace in Figure 1 confirms it is Gln272Ter, legacy for Gln298Ter). 0.5pt (PM3_supporting). GT28 is compound heterozygous for Gln298Ter and c.1728del (Classified Pathogenic by the PD-VCEP). Confirmation of trans phase was not reported. Not considered here to avoid circularity.","Number of Patients":1,"In trans Variants":["p.Gln298Ter c.(892C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA273108","Variant Name":"NM_000277.1:c.898G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21147011,"Raw Comment":"A300S in trans with c.1066-11G>A (VarID 607, Pathogenic in ClinVar) in 10 patients. Homozygous in 9 patients. Detected with p.R261Q in 6 patients. With IVS7+4A>G in 2 patients. with p.L48S in 2 patients. with p.R176X in 2 patients. with 8 other mutations in 8 patients.","Number of Patients":10,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229666","Variant Name":"NM_000277.1:c.631C>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21147011,"Raw Comment":"p.P211T was seen with IVS10-11G>A (VarID 607, Pathogenic) in 4 patients.","Number of Patients":4,"In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16021007","Variant Name":"NM_000277.1:c.197_204del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":21147011,"Raw Comment":"Allele 1:p.D75X, Allele 2: p.A300S (VarID92751, Pathogenic)","Number of Patients":1,"In trans Variants":["p.A300S c.(898G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA286506","Variant Name":"NM_000277.1:c.688G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21147011,"Raw Comment":"V230I found in 6 patients with PKU: 2 mHPA patients in trans with IVS10-11G>A (varID 607, Pathogenic); 1 mPKU patient in trans with p.L48S (varID 608, Pathogenic); 1 mHPA patient in trans with p.R408W (varID 577, Pathogenic); 1 mHPA patient in trans with p.E390G (varID 625, Pathogenic\/LP); 1 mHPA patient in trans with IVS2+5G>C.","Number of Patients":6,"In trans Variants":["IVS2+5G>C","p.R408W c.(1222C>T)","p.L48S c.(143T>C)","IVS10-11G>A","p.E390G c.(1169A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA273109","Variant Name":"NM_000277.1:c.638T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21147011,"Raw Comment":"Detected in 2 patients: p.L213P\/p.E390G (VarID 625 P\/LP) and p.L213P\/p.D415N (VarID 617, Pathogenic).","Number of Patients":2,"In trans Variants":["p.E390G c.(1169A>G)","p.D415N c.(1243G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229350","Variant Name":"NM_000277.1:c.1114A>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21147011,"Raw Comment":"Seen in 1 patient, homozygous. Seen in 2nd patient with R408W (VarID577, Pathogenic). Seen in 3rd patient with IVS10-11G>A (VarID607, Pathogenic).","Number of Patients":3,"In trans Variants":["p.R408W c.(1222C>T)","IVS10-11G>A","homozygous c.1114A>T p.(Thr372Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA220582","Variant Name":"NM_000277.2:c.355C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21147011,"Raw Comment":"in trans with R261Q","Number of Patients":1,"In trans Variants":["p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229460","Variant Name":"NM_000277.2:c.169-13T>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21147011,"Raw Comment":"IVS2-13T>G seen with IVS10-11G>A (VarID 607, Pathogenic).","Number of Patients":1,"In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229876","Variant Name":"NM_000277.1:c.967_969delACA","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21147011,"Raw Comment":"T323del seen in 2 PKU patients. Once with P281L (VarID589, Pathogenic); once with L48S (VarID608, Pathogenic).","Number of Patients":2,"In trans Variants":["p.L48S c.(143T>C)","p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229426","Variant Name":"NM_000277.1:c.1289T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21147011,"Raw Comment":"L430P found in trans with A300S (VarID 92751, Pathogenic in ClinVar) in 1 PKU patient, and R241C (VarID 102803, Pathogenic in ClinVar) in 1 PKU patient.","Number of Patients":2,"In trans Variants":["p.A300S c.(898G>T)","p.R241C c.(721C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA114367","Variant Name":"NM_000277.1:c.1169A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21147011,"Raw Comment":"8 homozygotes reported","Number of Patients":8,"In trans Variants":["homozygous c.1169A>G p.(Glu390Gly)"],"labels":"fine-tune"},{"CinGen ID":"CA229341","Variant Name":"NM_000277.1:c.1097C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21147011,"Raw Comment":"Seen in trans with P281L (VarID 589, Pathogenic)","Number of Patients":1,"In trans Variants":["p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA267634","Variant Name":"NM_000277.2:c.1196T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21147011,"Raw Comment":"V399A detected with P281L in 1 patient and p.E178G in another patient.","Number of Patients":2,"In trans Variants":["p.P281L c.(842C>T)","p.E178G c.(533A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229891","Variant Name":"NM_000277.1:c.982A>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":21147011,"Raw Comment":"T328A seen in trans in 1 PKU patient with L48S (VarID 608, Pathogenic).","Number of Patients":1,"In trans Variants":["p.L48S c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229459","Variant Name":"NM_000277.2:c.168G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21147011,"Raw Comment":"E56D seen in trans with p.Y356X in 1 patient, and p.R408W (VarID 577, Pathogenic) in another patient","Number of Patients":2,"In trans Variants":["p.R408W c.(1222C>T)","p.Y356X"],"labels":"fine-tune"},{"CinGen ID":"CA645372267","Variant Name":"NM_000277.1:c.835_836delinsTG","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":21147011,"Raw Comment":"P279C seen with R408W (VarID 577, Pathogenic in ClinVar) in 1 patient","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229681","Variant Name":"NM_000277.1:c.665A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":21147011,"Raw Comment":"D222V found in trans with p.R243X (VarID R243X, Pathogenic) in patient with classic PKU, and p.R241H (VarID 102804, Pathogenic) in another patient with mHPA.","Number of Patients":2,"In trans Variants":["p.R241H c.(722G>A)","p.R243X"],"labels":"fine-tune"},{"CinGen ID":"CA229401","Variant Name":"NM_000277.3:c.121C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":21147011,"Raw Comment":"L41F seen in trans with IVS10-11G>A (VarID 607, Pathogenic in ClinVar)","Number of Patients":1,"In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229718","Variant Name":"NM_000277.1:c.724C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21147011,"Raw Comment":"Reported in 1 patient with IVS10-11G>A (VarID 607, Pathogenic)","Number of Patients":1,"In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA220578","Variant Name":"NM_000277.2:c.169G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":21147011,"Raw Comment":"Genotype: p.E57K\/p.V388M (VarID619, Path) from supplementary table.","Number of Patients":1,"In trans Variants":["p.V388M c.(1162G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA16020870","Variant Name":"NM_000277.1:c.842+4A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":21147011,"Raw Comment":"Seen in 2 patients in with A300S (VarID 92751, Pathogenic)","Number of Patients":2,"In trans Variants":["p.A300S c.(898G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA891862634","Variant Name":"NM_000277.1:c.47_48insCT","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21147011,"Raw Comment":"It was also noted in 3 Turkish probands: in two, it was found in trans with the p.R243X allele, and in one, it was found in trans with the p.R261Q allele (PMID: 21147011); all three cases had classic as assessed by plasma Phe levels and BH4 deficiency was excluded by genetic testing.","Number of Patients":3,"In trans Variants":["p.R261Q c.(782G>A)","p.R243X"],"labels":"fine-tune"},{"CinGen ID":"CA229414","Variant Name":"NM_000277.1:c.1238G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":21307867,"Raw Comment":"A132V (not in ClinVar) \/R413P. Two patients with compound heterozygote mutations of V388M (VarID619, Pathogenic) \/R413P.","Number of Patients":3,"In trans Variants":["p.V388M c.(1162G>A)","p.A132V c.(395C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":21366435,"Raw Comment":"From a cohort of 51 hearing impaired individuals from 46 families, identified one homozygous individual.","Number of Patients":1,"In trans Variants":["homozygous c.1229C>T p.(Thr410Met)"],"labels":"fine-tune"},{"CinGen ID":"CA10576905","Variant Name":"NM_000260.4(MYO7A):c.6062A>G","Condition":"Usher syndrome type 1","Criterion":"PM3","PMID":21436283,"Raw Comment":"Variant was reported in an individual from France with Usher Syndrome 1. This variant was found in the compound heterozygous state with another variant (NM_000260.4(MYO7A):c.722G>A p.Arg241His), which is pathogenic\/likely pathogenic. Phase was not reported (0.5 points; PM3; PMID: 21436283). Variant was found in the homozygous state at least two children (boy age nine and girl age thirteen) from the same family, each of whom had sensorineural hearing loss with early symptoms of retinal degeneration. The parents were consanguineous (0.25 points; PM3; Allam, 2014). In another family, this variant was found in the homozygous state in a male adolescent, 14 years of age, with bilateral congenital hearing loss, trouble seeing at night, and chronic pain in the throat (0.5 points; PM3; Allam, 2014). ","Number of Patients":"err","In trans Variants":["c.722G>A p.Arg241His"],"labels":"fine-tune"},{"CinGen ID":"CA8815664","Variant Name":"NM_000152.4:c.2237G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Very Strong","PMID":21484825,"Raw Comment":"Patient 1 is compound heterozygous for c.2237G>A (p.Trp746Ter) and c.853C>T (p.Pro285Ser). c.853C>T (p.Pro285Ser) is likely pathogenic based on assessment by the ClinGen VCEp. The phase of the variants was not confirmed. This patient meets PP4 criteria. However, c.2237G>A (p.Trp746Ter) was used to calculate PM3 strength for c.853C>T (p.Pro285Ser) so PM3 was not used here to avoid a circular dependency.","Number of Patients":1,"In trans Variants":["c.853C>T p.Pro285Ser"],"labels":"fine-tune"},{"CinGen ID":"CA401364275","Variant Name":"NM_000152.5:c.953T>A","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":21484825,"Raw Comment":"This variant has been detected in at least 2 individuals with Pompe disease. Of those individuals, 1 was compound heterozygous for the variant and a pathogenic variant, c.1822C>T (p.Arg608Ter) (PMID 21484825) (0.5 pt, PM3_Supporting).","Number of Patients":2,"In trans Variants":["c.1822C>T p.Arg608Ter"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":21551164,"Raw Comment":"This study identified a 46 year old Caucasian female who was diagnosed with Pendred syndrome. \"This case illustrates that, although pendrin is not usually required to maintain acid\u00e2\u0080\u0093base\nhomeostasis under ambient condition, loss of renal bicarbonate excretion by pendrin during a\nmetabolic alkalotic challenge may contribute to life-threatening acid\u00e2\u0080\u0093base disturbances in patients\nwith Pendred syndrome\". This patient was homzoygous for the variant. Sequencing of the SLC26A4 gene revealed the genoytype. Consanguinity was not discussed.","Number of Patients":1,"In trans Variants":["homozygous c.412G>T p.(Val138Phe)"],"labels":"eval"},{"CinGen ID":"CA8603182","Variant Name":"NM_000419.4:c.1234G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Strong","PMID":21557682,"Raw Comment":"The proband is compound heterozygous for the paternally inherited Likely Pathogenic variant c.1073G>A (p.Arg358His) variant and the maternally inherited c.1234G>A (p.Gly412Arg) variant. 1pt","Number of Patients":1,"In trans Variants":["c.1073G>A p.Arg358His"],"labels":"fine-tune"},{"CinGen ID":"CA380144219","Variant Name":"NM_000536.4:c.193G>T","Condition":"recombinase activating gene 2 deficiency","Criterion":"PM3-Supporting","PMID":21624848,"Raw Comment":"One individual with SCID was homozygous of this variant (0.5pt, PMID 21624848). 0.5pt in total, PM3_Supporting is met.","Number of Patients":1,"In trans Variants":["homozygous c.193G>T p.(Asp65Tyr)"],"labels":"fine-tune"},{"CinGen ID":"CA382534080","Variant Name":"NM_000051.3:c.1442T>G","Condition":"hereditary breast cancer","Criterion":"PM3-Strong","PMID":21665257,"Raw Comment":"This variant has been observed in a compound heterozygous state (confirmed) in one individual with Ataxia-Telangiectasia (PMID 21665257: PM3_Strong) (4 POINTS)","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA8815236","Variant Name":"NM_000152.4:c.1222A>G","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":21687968,"Raw Comment":"This variant was found in patient 8 with c.1000G>A. This patient did not meet PP4 criteria.","Number of Patients":1,"In trans Variants":["c.1000G>A p.(Gly334Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA273356","Variant Name":"NM_000277.2:c.745C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21871829,"Raw Comment":"L249F found with p.R261X (Pathogenic) in Patient 47. p.A309V (Path\/LP) in Patient 48, p.V388M (Pathogenic) in Patient 49.","Number of Patients":3,"In trans Variants":["p.V388M c.(1162G>A)","p.R261X","p.A309V c.(926C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229775","Variant Name":"NM_000277.1:c.805A>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21871829,"Raw Comment":"Patients 19, 20: R261X\/I269L (previously described). Patient 55: p.I269L\/IVS10nt-11G>A (VarID 607, pathogenic)","Number of Patients":3,"In trans Variants":["p.R261X","IVS10nt-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229781","Variant Name":"NM_000277.2:c.809G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21871829,"Raw Comment":"Seen in multiple patients with classic PKU (>1200uM). In homozgotes state and in trans with IVS10nt-11G>A, L348K, S349P, R158Q, E390G, D415N. Predicted residual enzyme activity >1.","Number of Patients":"NA","In trans Variants":["homozygous c.809G>A p.(Arg270Lys)","p.S349P c.(1045T>C)","p.D415N c.(1243G>A)","p.R158Q c.(473G>A)","p.E390G c.(1169A>G)","IVS10nt-11G>A","p.L348K"],"labels":"fine-tune"},{"CinGen ID":"CA114362","Variant Name":"NM_000277.1:c.1241A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":21871829,"Raw Comment":"compound het patients","Number of Patients":"NA","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA16020979","Variant Name":"NM_000277.1:c.1244A>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":21890392,"Raw Comment":"D415V was found in trans with c.47_48delCT, p.S16XfsX1 (VarID 102696, Pathogenic\/LP) in 1 patient and c.1066 \u00e2\u0088\u0092 11G > A (VarID 607, Pathogenic) in another patient. Mutations were confirmed by carrier analysis of parents and\/or siblings.","Number of Patients":2,"In trans Variants":["c.47_48delCT p.S16XfsX1","c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16020946","Variant Name":"NM_000277.3:c.1129T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":21890392,"Raw Comment":"PMID: 21890392 - This patient (case #8) carried the previously described variant c.1066-11G>A (VarID 607, P, 10 submitters) which was inherited on the paternal allele. Y377D inherited on the maternal allele. = 1.0 point","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA397722617","Variant Name":"NM_000018.4:c.339C>A","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3","PMID":21932095,"Raw Comment":"PM3 is met. This variant has been detected in one individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This individual was reported as compound heterozygous for the variant and a distinct pathogenic variant and was confirmed in trans by parental testing (PM3 points = 1.0; PMID: 21932095; c.848T>C p.(Val243Ala) ClinVar Variation ID: 21025) (PM3).","Number of Patients":1,"In trans Variants":["c.848T>C p.Val243Ala"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":21961810,"Raw Comment":"This study investigated 144 patients with SNHL adn temporal bone malformations and found that 6 patients had the p.T410M variant. There was one comp. het. indiviudal with a p.A360V variant in trans, 4 compound het individuals with the c.919-2 A>G splice variant, 1 individual with the p.SF532, 545* variant, and one indivudal with the c.1343C>A p.S448X variant.","Number of Patients":12,"In trans Variants":["p.A360V c.(1079C>T)","c.(919-2 A>G)","p.(SF532,545*) c.1594AG>T","c.1343C>A p.S448X"],"labels":"eval"},{"CinGen ID":"CA229461","Variant Name":"NM_000277.2:c.169_171del","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":22106832,"Raw Comment":"A compound heterozygous patient is described with this c.169_171del variant and the c.1066-11G>A (ClinVar 607, Pathogenic) variant.","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229545","Variant Name":"NM_000277.2:c.441+1G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":22112818,"Raw Comment":"1 case with classic PKU, found in trans with R408W allele","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA180669","Variant Name":"NM_000260.4:c.2476G>A","Condition":"Usher syndrome","Criterion":"PM3","PMID":22135276,"Raw Comment":"188 individuals with Usher were tested for variants in MYO7A, CDH23, PCDH15,\nUSH1C, USH1G, USH2A, GPR98, WHRN, CLRN1, and SLC4A7. The p.Ala826Thr variant was identified in 1 Caucasian compound heterozygous individual who also harbored the p.Trp1431X variant.","Number of Patients":1,"In trans Variants":["p.Trp1431X"],"labels":"eval"},{"CinGen ID":"CA262054","Variant Name":"NM_206933.2:c.1036A>C","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":22135276,"Raw Comment":"detected in trans with p.Glu3305ArgfsX41, p.Trp3521Arg, and Lys419Phe","Number of Patients":1,"In trans Variants":["p.Glu3305ArgfsX41","p.Trp3521Arg c.(10561T>A)","p.Lys419Phe"],"labels":"eval"},{"CinGen ID":"CA273289","Variant Name":"NM_206933.2:c.4510dupA","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":22135276,"Raw Comment":"Total: 3 Path variants in trans. The variant was detected in a proband from a UK study with Usher type 2 in trans with the p.Trp2744X variant. The variant was also identified in two more USH2A patients, one with a p.Cys419Phe which is a P\/LP variant and another in a proband with the p.Glu767SerfsX21 variant. Patients were recruited through Moorfields Eye Hospital which was also the case of the patient described in Carss 2017, though that proband was not counted because the other allele was not identified.","Number of Patients":3,"In trans Variants":["p.Cys419Phe c.(1256G>T)","p.Glu767SerfsX21"],"labels":"eval"},{"CinGen ID":"CA143283","Variant Name":"NM_206933.3:c.12295-3T>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":22135276,"Raw Comment":"Indian proband diagnosed with Usher type 2 --> 0.5 points (phase unknown) - other variant is p.Glu767Serfs*21","Number of Patients":1,"In trans Variants":["p.Glu767Serfs*21"],"labels":"eval"},{"CinGen ID":"CA290947544","Variant Name":"NM_000419.4:c.2333A>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":22190468,"Raw Comment":"Patient 3 is compound heterozygous, with phase confirmation, for this variant and c.2975del, which is classified as likely pathogenic by the Platelet Disorders VCEP. A score of 1 point is applied toward PM3 scoring, according to the SVI recommendation.","Number of Patients":1,"In trans Variants":["c.2975del p.(Glu992Glyfs*?)"],"labels":"fine-tune"},{"CinGen ID":"CA626224451","Variant Name":"NM_000419.4:c.2975del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":22190468,"Raw Comment":"The variant is found in trans (confirmed by haplotype analysis) with Gln778Pro in Patient 3 from PMID: 22190468. Gln778Pro is classified Pathogenic (PM3).","Number of Patients":1,"In trans Variants":["p.Gln778Pro c.(2333A>C)"],"labels":"fine-tune"},{"CinGen ID":"CA274281","Variant Name":"NM_000152.3:c.1548G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":22237443,"Raw Comment":"Patient 4 is compound heterozygous for c.1548G>A (p.Trp516Ter) and the known pathogenic variant c.525delT. The phase of the variants is unknown. This patient has no residual GAA activity in fibroblasts. (0.5 points)","Number of Patients":1,"In trans Variants":["c.525delT p.(Glu176Argfs*45)"],"labels":"eval"},{"CinGen ID":"CA274311","Variant Name":"NM_000152.4:c.1128_1129delGGinsC","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":22237443,"Raw Comment":"c.1128_1129delGGinsC was found in compound heterozygosity with a pathogenic variant, c.2237G>A (p.Trp746Ter), in an individual with infantile onset Pompe disease and \"absent\" GAA activity. c.2237G>A (p.Trp746Ter) has been classified as pathogenic by multiple ClinVar submitters and by the ClinGen LSd VCEP (note that c.2237G>A can be classified as pathogenic without including data for c.1128_1129delGGinsC, thus avoiding a circular argument). The phase of the variants is unknown in this patient. Based on the ClinGen LSD VCEP guidelines for assessing strength of evidence for PM3, 0.5 points were awarded.","Number of Patients":1,"In trans Variants":["c.2237G>A (p.Trp746Ter)"],"labels":"eval"},{"CinGen ID":"CA8815664","Variant Name":"NM_000152.4:c.2237G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Very Strong","PMID":22237443,"Raw Comment":"Patient 2 is compound heterozygous for c.2237G>A (p.Trp746Ter) and c.1128_1129delinsC. c.1128_1129delinsC is pathogenic based on assessment by the ClinGen LSD VCEP. The phase of the variants was not confirmed. This patient meets PP4 criteria. However, c.2237G>A (p.Trp746Ter) was used to calculate PM3 strength for c.1128_1129delinsC so PM3 was not used here to avoid a circular dependency.","Number of Patients":1,"In trans Variants":["c.1128_1129delinsC p.(Trp376Cysfs*16)"],"labels":"eval"},{"CinGen ID":"CA658795282","Variant Name":"NM_000152.5:c.2300del","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":22252923,"Raw Comment":"One patient has been reported who is homozygous for the variant (PMID 22252923, personal communication). 0.5 points, PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2300del p.(Phe767Serfs*14)"],"labels":"eval"},{"CinGen ID":"CA341869","Variant Name":"NM_001482.3:c.484+1G>T","Condition":"AGAT deficiency","Criterion":"PM3-Supporting","PMID":22386973,"Raw Comment":"The c.484+1G>T variant in GATM has been previously reported in an individual (PMID: 22386973) who showed significantly decreased creatine peak on H1-MRS, nondetectable enzyme activity in cultured lymphoblasts, and low GAA in plasma and low creatine in plasma (5 points total; PP4_Strong) and was homozygous for the variant (PM3_Supporting). Both of her parents were confirmed by follow-up genetic testing to be heterozygous for the variant.","Number of Patients":1,"In trans Variants":["homozygous c.484+1G>T "],"labels":"fine-tune"},{"CinGen ID":"CA229610","Variant Name":"NM_000277.3:c.529G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":22391997,"Raw Comment":"Patient 5, Allele 2: p.R261Q. Patient 8, Allele 2: p.F55fs. parental testing not reported.","Number of Patients":2,"In trans Variants":["p.F55fs","p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA399806881","Variant Name":"NM_000419.5:c.131G>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":22394243,"Raw Comment":"Proband from PMID: 22394243 is compound heterozygous for c.1440-13_1440-1del and Gly44Val, confirmed in trans. 1pt","Number of Patients":1,"In trans Variants":["p.Gly44Val c.(131G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229610","Variant Name":"NM_000277.3:c.529G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":22513348,"Raw Comment":"Patient 50: p.R158Q\/p.V177L. parental testing not reported.","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA16020739","Variant Name":"NM_000277.1:c.185T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":22513348,"Raw Comment":"Patient 38: allele 1:p.L62P, allele 2: R408W.","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA267654","Variant Name":"NM_000277.2:c.441+6T>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":22526846,"Raw Comment":"Detected in trans with likely pathogenic p.P281L (ClinVar 589), and c.1315+1G>A (ClinVar 576). Family segregation was consistent with autosomal recessive inheritance.","Number of Patients":"2","In trans Variants":["p.P281L c.(842C>T)","c.1315+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229357","Variant Name":"NM_000277.3:c.1130A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":22526846,"Raw Comment":"The variant has been previously reported in trans with p.R243* (Pathogenic in ClinVar and per ClinGen PAH VCEP) in a PKU patient (plasma Phe 765 umol\/L); BH4 deficiency was excluded by analysis of urinary pterins and dihydropterine reductase assays (PMID: 22526846) (PM3; PP4_Moderate).","Number of Patients":1,"In trans Variants":["p.R243* c.(727C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA114362","Variant Name":"NM_000277.1:c.1241A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":22526846,"Raw Comment":"reported in 9 patients (2 homozygous). Both homozygous patients with Phe levels 300-400 (Mild Hyperphenylalanemia), other patients with variable Phe levels depending on 2nd variant. One paBH4 defect excluded in all patients** (PP4_strong-specific analyte with other biochemical causes ruled out)\nPatient #41 p.R408W \/ p.Y414C, Phe 744 @dx (PM3 (in trans with known pathogenic variant)","Number of Patients":9,"In trans Variants":["p.R408W c.(1222C>T)","homozygous c.1241A>G p.(Tyr414Cys)","p.Y414C c.(1241A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA274024","Variant Name":"NM_000152.4:c.1051delG","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":22676651,"Raw Comment":"This variant was found in patient 4 with c.-32-13T>G. c.-32-13T>G is a well known pathogenic variant. The phase of the variants was not confirmed. This patient meets PP4 criteria. No points were awarded since in trans data for c.-32-13T>G has already been scored and the variants were not confirmed in trans.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA8814791","Variant Name":"NM_000152.3:c.118C>T","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":22676651,"Raw Comment":"Patient 12 is compound heterozygous for c.118C>T (p.Arg40Ter) and c.-32-13T>G. The phase of the variants is unknown. GAA activity in lymphocytes is 0.5 (normal range of 9-42 nmole\/mg\/hr). (0.5 points)","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA294896907","Variant Name":"NM_000152.5:c.1962_1964del","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":22711147,"Raw Comment":"The paper describes an Indian family with a previously child affected by infantile onset Pompe disease who passed away. No genetic testing was performed on the child and no results for residual GAA activity are provided. Both parents are heterozygous for a variant in GAA; one for p.Gly655del and one for p.Asp489Asn. It is unlcear whether this family is also reported in PMID 22791670.","Number of Patients":0,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA16020949","Variant Name":"NM_000277.2:c.1147C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":22763404,"Raw Comment":"homozygote with classic PKU","Number of Patients":1,"In trans Variants":["homozygous c.1147C>T p.(Gln383*)"],"labels":"fine-tune"},{"CinGen ID":"CA294896907","Variant Name":"NM_000152.5:c.1962_1964del","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":22791670,"Raw Comment":"A patient is described who is compound heterozygous for p.Gln355del and p.Asp489Asn (from the data, it is not clear if one or two patients have this genotype). The range of GAA activity, measured in skin fibroblasts, for these patients is 2.4-5.6 nmol\/h\/mg; reference range not provided. p.Asp489Asn has multiple submitters in ClinVar and is classified as pathogenic\/likely pathogenic.","Number of Patients":1,"In trans Variants":["p.Asp489Asn c.(1465G>A)","p.Gln355del"],"labels":"fine-tune"},{"CinGen ID":"CA399790478","Variant Name":"NM_000419.5:c.2933G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":22837472,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. This individual was compound heterozygous for this variant and the NM_000419.5(ITGA2B):c.2994G>A (p.Trp998Ter) variant, which was classified as Pathogenic by the PD VCEP. The phase of the variants in this proband is unknown (0.5 PM3 points, PMID: 22837472, PM3_Supporting). ","Number of Patients":1,"In trans Variants":["c.2994G>A p.Trp998Ter"],"labels":"fine-tune"},{"CinGen ID":"CA229341","Variant Name":"NM_000277.1:c.1097C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":22841515,"Raw Comment":"Patient 106: c.1066-11 G>A (VarID 607, Pathogenic) \/p.P366H.","Number of Patients":1,"In trans Variants":["c.1066-11G>A p.P366H"],"labels":"eval"},{"CinGen ID":"CA397722484","Variant Name":"NM_000018.4:c.277+2T>G","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3","PMID":22847164,"Raw Comment":"PM3 is met. This variant has been detected in one individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This individual was compound heterozygous for the variant and a pathogenic or likely pathogenic variant was confirmed in trans by parental testing (c.388_390del; \nVCV000001626.12; PM3 points = 1.0, PMID:22847164) (PM3).","Number of Patients":1,"In trans Variants":["c.388\\_390del"],"labels":"fine-tune"},{"CinGen ID":"CA253338","Variant Name":"NM_022124.5:c.719C>T","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Strong","PMID":22899989,"Raw Comment":"12 probands cmpound het with rare VUS. Patients with phase confirmed reported in Wagatsuma 2007.","Number of Patients":12,"In trans Variants":["p.P240L c.(719C>T)","p.R301Q c.(902G>A)","p.R2029W c.(6085C>T)","p.Q1716P c.(5147A>C)","p.E956K c.(2866G>A)","p.T1368M c.(4103C>T)","p.N2287K c.(6861T>A)","p.E2438K c.(7312G>A)"],"labels":"eval"},{"CinGen ID":"CA16020744","Variant Name":"NM_000277.1:c.196G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":22921945,"Raw Comment":"Detected with p.S349P (VarID615, P\/LP) parental analysis not confirmed PMID: 22921945","Number of Patients":"1","In trans Variants":["p.S349P","c.(1045T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA10605404","Variant Name":"NM_000152.3:c.2501_2502delCA","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":22958975,"Raw Comment":"Patient 3, 8, and 9 are compound heterozygotes for c.2501_2502delCA and c.-32-13T>G in GAA, a known pathogenic variant. However, the phase of the variants was not confirmed. These patients also meet the PP4 criterion (0.5 points).","Number of Patients":3,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA8814791","Variant Name":"NM_000152.3:c.118C>T","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":22958975,"Raw Comment":"Patient 7 is compound heterozygous for c.118C>T (p.Arg40Ter) and c-32-13T>G and has 3.6% residual GAA activity (presumably in fibroblasts but tissue not stated). The phase of the variants is unknown. This data is not included because another patient with the same genotype, phase not confirmed, has already been included.","Number of Patients":1,"In trans Variants":["c-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA8815726","Variant Name":"NM_000152.5:c.2395C>T","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":22958975,"Raw Comment":"LOPD patient #1 (PMID: 22958975) has this variant in compound het with c.-32-13T>G. phase unknown. 0.5 points. Thus met PM3_Supporting. ","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA229395","Variant Name":"NM_000277.2:c.1200-8G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":23062575,"Raw Comment":"Patient 2 genotype: IVS11-8G>A\/p.A403V. Parental analysis not reported.","Number of Patients":1,"In trans Variants":["p.A403V c.(1208C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229527","Variant Name":"NM_000277.2:c.386A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":23062575,"Raw Comment":"Patient 5 genotype: p.D129G \/ p.R408W. Parental segregation not reported\/performed.","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16608977","Variant Name":"NM_000215.4:c.349C>T","Condition":"T-B+ severe combined immunodeficiency due to JAK3 deficiency","Criterion":"PM3-Supporting","PMID":23069490,"Raw Comment":"one homozygous patient, 0.5pts, PM3_Supporting (PMID: 23069490).","Number of Patients":1,"In trans Variants":["homozygous c.349C>T p.(Arg117Cys)"],"labels":"fine-tune"},{"CinGen ID":"CA229622","Variant Name":"NM_000277.2:c.559T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23074961,"Raw Comment":"found in 1 case, in trans with p.R261Q (established pathogenic allele); phenotype not mentioned","Number of Patients":1,"In trans Variants":["p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA261445","Variant Name":"NM_000441.1:c.919-2A>G","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":23151025,"Raw Comment":"Retrospective review of 1065 Chinese probands with moderate-to-profound bilateral sensorineural hearing loss found 53 homozygous and 80 heterozygous for the c.919-2A>G variant. 16 individuals were compound het. for the pathogenic p.H723R variant in SLC26A4.","Number of Patients":69,"In trans Variants":["homozygous c.919-2A>G","p.H723R c.(2168A>G)"],"labels":"eval"},{"CinGen ID":"CA16608675","Variant Name":"NM_000152.4:c.1478C>T","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":23160972,"Raw Comment":"Patient 2 is a compound heterozygote for c.1478C>T and c.1655T>C in GAA. The phase of the variants was not confirmed. GAA activity in the patient was not specified (0 points).","Number of Patients":1,"In trans Variants":["c.1655T>C p.(Leu552Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA253314","Variant Name":"NM_000441.1:c.-103T>C","Condition":"Pendred syndrome","Criterion":"PM3","PMID":23208854,"Raw Comment":"24 patients with AR, prelingual moderate to profound NSHL were sequenced. In one proband, the -103T>C variant was identified in heterozygosity. The proband also carried a heterozygous OTOF variant p.R794H.","Number of Patients":1,"In trans Variants":["p.R794H"],"labels":"fine-tune"},{"CinGen ID":"CA16020800","Variant Name":"NM_000277.3:c.494C>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":23225039,"Raw Comment":"Individuals with R111X\/A165D and R176X\/A165D genotypes, on the other hand, respectively presented moderate and classic PKU phenotypes.","Number of Patients":2,"In trans Variants":["p.R111X","p.R176X"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":23273637,"Raw Comment":"This paper identified the V138F variant in a Brazilian patient with NSHL and EVA. THe patient had a compound heterozygous genotype with the variant in trans with a p.Q413R variant which has been classified as LP by counsyl in 2016.","Number of Patients":1,"In trans Variants":["p.Q413R c.(1238A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA16020802","Variant Name":"NM_001354304.2:c.499A>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23357515,"Raw Comment":"This variant was detected 1 time with the pathogenic PAH variant p.Arg408Trp in a patient with PAH deficiency. It was not specified whether the patient's genotype was homozygous or compound heterozygous for the variant. PMID: 23357515","Number of Patients":1,"In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA6748708","Variant Name":"NM_000277.1:c.1218A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":23357515,"Raw Comment":"2 patients with the genotype p.[Ile406Met];[Arg408Trp] (VarID 577, Pathogenic).","Number of Patients":2,"In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020825","Variant Name":"NM_001354304.2:c.599C>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23357515,"Raw Comment":"This variant was detected with the pathogenic PAH variant p.Arg243*. It was not specified whether the parental analysis was performed. PMID: 23357515","Number of Patients":"NA","In trans Variants":["p.Arg243* c.(727C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020857","Variant Name":"NM_000277.1:c.788T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":23357515,"Raw Comment":"Based on our analysis, we predict that p.(Phe263Ser) causes significant impairment of the protein structure and function, and that patients carrying this mutation have the classical PKU phenotype (like our patient with the genotype p.[Phe263Ser];[c.1066-11 G > A]).","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229620","Variant Name":"NM_000277.3:c.556del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23357515,"Raw Comment":"p.[Arg408Trp]; [Thr186Hisfs*9]. Segregation analysis was not done, so phase is unknown. PMID: 23357515","Number of Patients":"NA","In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229527","Variant Name":"NM_000277.2:c.386A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":23357515,"Raw Comment":"detected in the homozygous state. Parental segregation not reported\/performed.","Number of Patients":1,"In trans Variants":["homozygous c.386A>G p.(Asp129Gly)"],"labels":"fine-tune"},{"CinGen ID":"CA214096","Variant Name":"NM_000215.4:c.678_679del","Condition":"T-B+ severe combined immunodeficiency due to JAK3 deficiency","Criterion":"PM3-Supporting","PMID":23384681,"Raw Comment":"One patient compound heterozygous with variant c.1767C>T (PMID: 23384681). It was not evaluated at this moment because the pathogenic level was already reached. \nOne homozygous patient described on ClinVar (3billion, T-B+ severe combined immunodeficiency due to JAK3 deficiency) affected status: yes. Hepatosplenomegaly (present), Pneumonia (present) - (0.5pt). PM3_Supporting.","Number of Patients":2,"In trans Variants":["c.1767C>T p.(=)"],"labels":"eval"},{"CinGen ID":"CA229610","Variant Name":"NM_000277.3:c.529G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":23430918,"Raw Comment":"p.V177L: p.R408W. parental testing not reported.","Number of Patients":"NA","In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229814","Variant Name":"NM_000277.2:c.842+3G>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23430918,"Raw Comment":"Genotype: c.842+3G>C: p.R408W (VarID 577, Pathogenic)","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229598","Variant Name":"NM_000277.2:c.511G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23430918,"Raw Comment":"Patient Genotype: p.G171R\/ p.R408W","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA267673","Variant Name":"NM_000277.2:c.796A>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":23430918,"Raw Comment":"PAH genotype: p.V190A (VarID 102740, no clinical significance provided): p.T266P.","Number of Patients":1,"In trans Variants":["p.V190A c.(569T>C)","p.T266P c.(796A>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229613","Variant Name":"NM_000277.2:c.535T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":23430918,"Raw Comment":"Patient genotype: p.Y179N: c.1066-11G>A","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229361","Variant Name":"NM_000277.3:c.1156T>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23430918,"Raw Comment":"PMID: 23430918 - Y386D detected with R158Q - reported as pathogenic in ClinVar (VarID:587), 14 submitters, phase unknown - 0.5 points","Number of Patients":0,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229570","Variant Name":"NM_000277.2:c.472C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23430918,"Raw Comment":"Table 2. Mutant Genotypes. p.R158W: p.R261P (VarID102832, LP). p.R158W: p.R408W (VarID577, Path). p.I65T (VarID:636, P\/LP): p.R158W.","Number of Patients":3,"In trans Variants":["p.R408W c.(1222C>T)","p.R261P c.(782G>C)","p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229500","Variant Name":"NM_000277.2:c.250G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":23430918,"Raw Comment":"mutant PAH Genotype p.D84Y: p.P281L (VarID589, pathogenic)","Number of Patients":1,"In trans Variants":["p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020746","Variant Name":"NM_000277.3:c.206dup","Condition":"phenylketonuria","Criterion":"PM3","PMID":23430918,"Raw Comment":"The c.206dupC variant in PAH has been previously reported as a heterozygous variant detected in trans with the known pathogenic c.1066-11G>A variant in a single Caucasian proband with classic PKU; BH4 deficiency was not formally excluded (PMID: 23430918) (PM3) (PP4).","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229845","Variant Name":"NM_000277.2:c.912G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23500595,"Raw Comment":"Patient 45: p.Q304Q~p.R176L. Genomic DNA of patients and their families was obtained from 3 mL of EDTA blood sample","Number of Patients":1,"In trans Variants":["p.R176L c.(527G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA251534","Variant Name":"NM_000277.2:c.829T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":23500595,"Raw Comment":"Found in trans with L48S in two individual with Classic PKU.","Number of Patients":2,"In trans Variants":["p.L48S c.(143T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA251530","Variant Name":"NM_000277.2:c.473G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":23500595,"Raw Comment":"in trans with p.I48S","Number of Patients":1,"In trans Variants":["p.I48S"],"labels":"fine-tune"},{"CinGen ID":"CA16020936","Variant Name":"NM_000277.3:c.1081A>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23500595,"Raw Comment":"Detected with R243X (P, 6 submitters). Unsure if parental analysis was performed. PMID: 23500595","Number of Patients":1,"In trans Variants":["p.R243X"],"labels":"fine-tune"},{"CinGen ID":"CA251538","Variant Name":"NM_000277.1:c.1066-11G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23500595,"Raw Comment":"IVS10-11G>A was seen on 29 alleles. Patient 3: p.R243Q\/IVS10-11G>A (VarID591, Pathogenic). Patient 4: p.R243X\/IVS10-11G>A. (VarID588, Pathogenic). Patient 6: p.R261Q\/IVS10-11G>A (VarID582, P\/LP). Patient 8: p.R270K\/IVS10-11G>A (VarID102846, Pathogenic). Patient 10: p.I65T\/IVS10-11G>A (VarID636, P\/LP).","Number of Patients":5,"In trans Variants":["p.R243Q c.(728G>A)","p.R243X","p.R270K c.(809G>A)","p.I65T c.(194T>C)","p.R261Q c.(782G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA16020855","Variant Name":"NM_000277.1:c.773T>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23514811,"Raw Comment":"Table 3. Patient 14. p.L258P on both alleles. p.L258P is present in two mild PKU homozygous patients. Genetic analysis in parents confirmed that the patients are homozygous.","Number of Patients":2,"In trans Variants":["homozygous c.773T>C p.(Leu258Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA16020994","Variant Name":"NM_000277.3:c.1314_1315+4del","Condition":"phenylketonuria","Criterion":"PM3","PMID":23514811,"Raw Comment":"It has been reported in the published literature in one case (PMID: 23514811) with abnormal blood Phe and BH4 deficiency formally excluded (PP4_Moderate); in trans with the p.R138Q variant (Pathogenic per PAH VCEP) (PM3).","Number of Patients":1,"In trans Variants":["p.R138Q"],"labels":"fine-tune"},{"CinGen ID":"CA229532","Variant Name":"NM_000277.2:c.3G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23514811,"Raw Comment":"Genotype in 2 siblings: p.M1I\/F55L.","Number of Patients":2,"In trans Variants":["p.F55L c.(163T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229845","Variant Name":"NM_000277.2:c.912G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23514811,"Raw Comment":"Patient(s) genotype: p.I65T\/p.Q304Q detected in 2 unrelated patients. Patient 48: p.A300S\/p.Q304Q. Genomic DNA of patients and their families was obtained from whole blood samples.","Number of Patients":3,"In trans Variants":["p.A300S c.(898G>T)","p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA273112","Variant Name":"NM_000277.1:c.441+5G>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23514811,"Raw Comment":"IVS4 + 5g>t was seen in 7 patients. Twice in trans with IVS10-11g>a (VarID 607, Pathogenic) in unrelated patients with mild PKU. 5 times in trans with p.V388M (VarID 619, Pathogenic) in 1 patient with classic PKU and 4 patients with mild PKU, all unrelated.","Number of Patients":7,"In trans Variants":["p.V388M c.(1162G>A)","c.IVS10-11g>a"],"labels":"fine-tune"},{"CinGen ID":"CA229673","Variant Name":"NM_000277.1:c.649T>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23514811,"Raw Comment":"C217G found in trans with IVS10-11g>a in patient with mild PKU. (VarID 607, Pathogenic in ClinVar)","Number of Patients":1,"In trans Variants":["IVS10-11g>a"],"labels":"fine-tune"},{"CinGen ID":"CA229791","Variant Name":"NM_000277.2:c.824C>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":23514811,"Raw Comment":"Single patient, in trans I65T with moderate PKU (600-1200umol\/L)","Number of Patients":1,"In trans Variants":["p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229830","Variant Name":"NM_000277.2:c.865G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":23514811,"Raw Comment":"Single patient with mild PKU in trans wtih R155C, which has been curated by the Metabolism WG as Likely Pathogenic","Number of Patients":1,"In trans Variants":["p.R155C c.(463C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA275277","Variant Name":"NM_206933.2:c.8682-9A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":23591405,"Raw Comment":"1 sporadic cpd het with E4078EfsX20 (same individual in Baux 2007) with type 2 also harbors Val218Glu (neither classified ClinVar) not counted","Number of Patients":1,"In trans Variants":["p.Val218Glu c.(653T>A)"],"labels":"fine-tune"},{"CinGen ID":"CA10605404","Variant Name":"NM_000152.3:c.2501_2502delCA","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":23601496,"Raw Comment":"Subject E is a compound heterozygote for c.2501_2502delCA and c.1933G>A (p.Asp645Asn) in GAA. c.1933G>A (p.Asp645Asn) is pathogenic based on assessment by the ClinGen LSD VCEP. The phase of the variants was not confirmed. This patient also meets the PP4 criterion. However, in trans data from this patient was included in the classification of c.1933G>A (p.Asp645Asn), so no points were awarded to avoid a circular dependency.","Number of Patients":1,"In trans Variants":["c.1933G>A (p.Asp645Asn)"],"labels":"eval"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":23638949,"Raw Comment":"Identified 2 compound het individuals with p.H723R and p.V659L as the variants in trans with p.T410M","Number of Patients":2,"In trans Variants":["p.H723R c.(2168A>G)","p.V659L c.(1975G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229867","Variant Name":"NM_000277.1:c.941C>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":23690520,"Raw Comment":"Retrospective study, large cohort of patients. Specific genotypes found in supplementary table 1.","Number of Patients":"err","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229654","Variant Name":"NM_000277.1:c.612T>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23690520,"Raw Comment":"In trans with p.P211T (ClinVar, LP)","Number of Patients":1,"In trans Variants":["p.P211T c.(631C>A)"],"labels":"fine-tune"},{"CinGen ID":"CA262105","Variant Name":"NM_206933.2:c.5581G>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":23737954,"Raw Comment":"5 unrelated Chinese families with Usher syndrome were tested using a panel of 144 known genes for deep exome resequencing. The p.Gly1861Ser variant was identified in family F2 in trans with a novel frameshift c.8602delA, but was in cis with a second missense variant p.R5143C. The cis variants were also present in an unaffected sib.","Number of Patients":5,"In trans Variants":["c.8602delA p.(Asn2868Ilefs*6)"],"labels":"eval"},{"CinGen ID":"CA16020843","Variant Name":"NM_000277.1:c.697T>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23764561,"Raw Comment":"Mutation p.F233I was detected in two apparently unrelated patients in compound heterozygosity with p.R408W (VarID 577, Pathogenic) and p.V245A (Pathogenic) respectively.","Number of Patients":2,"In trans Variants":["p.R408W c.(1222C>T)","p.V245A c.(734T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229802","Variant Name":"NM_000277.2:c.833C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23764561,"Raw Comment":"Found in trans with R408W (VarID 577, Pathogenic in Clinvar) and P281L (VarID 589, Pathogenic in Clinvar)","Number of Patients":2,"In trans Variants":["p.R408W c.(1222C>T)","p.P281L c.(842C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229609","Variant Name":"NM_000277.2:c.529G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23764561,"Raw Comment":"Family 75 Genotype: IVS4+5G>T\/p.V177M; Family 77 Genotype: IVS12+1G>A\/p.V177M","Number of Patients":2,"In trans Variants":["IVS12+1G>A","IVS4+5G>T"],"labels":"fine-tune"},{"CinGen ID":"CA229264","Variant Name":"NM_000277.3:c.1006C>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23764561,"Raw Comment":"Patient 31 of PMID: 23764561 is compound heterozygous for Q336X and R408W (ClinVar 577 Pathogenic, reviewed by PAH VCEP). Confirmation of trans phase not reported.","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229596","Variant Name":"NM_000277.3:c.510-6T>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23764561,"Raw Comment":"Patient 51 of PMID: 23764561 is compound heterozygous for c.510-6T>G and R408W (ClinVar 577 Pathogenic, reviewed by PAH VCEP). Confirmation of trans phase not reported.","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA263244","Variant Name":"NM_001482.3:c.608A>C","Condition":"AGAT deficiency","Criterion":"PM3-Supporting","PMID":23770102,"Raw Comment":"The c.608A>C (p.Tyr203Ser) variant in GATM has been previously reported in two siblings who were homozygous for the variant; the parents, who were first cousins, were confirmed to be heterozygous (PMID: 23770102) (0.5 points) (PM3_Supporting).","Number of Patients":2,"In trans Variants":["homozygous c.608A>C p.(Tyr203Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA180669","Variant Name":"NM_000260.4:c.2476G>A","Condition":"Usher syndrome","Criterion":"PM3","PMID":23770805,"Raw Comment":"Of 243 Pakistani families with hearing loss, 34 consanguineous families with apparent linkage to MYO7A, CDH23, or SLC26A4 were tested for variants in 24 genes from the OtoSeq panel. The p.Ala826Thr variant was identified in homozygosity in one affected family. The proband was also homozygous for p.Gly434Arg. (A rare VUS)","Number of Patients":1,"In trans Variants":["homozygous c.2476G>A p.(Ala826Thr)"],"labels":"eval"},{"CinGen ID":"CA229679","Variant Name":"NM_000277.1:c.665A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23842451,"Raw Comment":"1 PKU patient had genotype c.1066-11G>A1\/p.D222G","Number of Patients":1,"In trans Variants":["c.1066-11G>A1"],"labels":"eval"},{"CinGen ID":"CA229604","Variant Name":"NM_000277.2:c.521T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":23842451,"Raw Comment":"patient genotype: p.I174T\/p.F299C (P\/LP, 6 submitters)","Number of Patients":1,"In trans Variants":["p.F299C c.(896T>G)"],"labels":"eval"},{"CinGen ID":"CA16020997","Variant Name":"NM_001354304.2:c.1318G>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23842451,"Raw Comment":"(PMID: 23842451) in presumed trans with the p.R243* mutation (Pathogenic per PAH VCEP) (0.5 points; PM3_Supporting).","Number of Patients":"err","In trans Variants":["p.R243* c.(727C>T)"],"labels":"eval"},{"CinGen ID":"CA16020833","Variant Name":"NM_000277.1:c.510-19_667del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23842451,"Raw Comment":"Patient genotype: c.510-21_665del\/G272* (VarID 596, Pathogenic)","Number of Patients":1,"In trans Variants":["G272* c.(814G>T)"],"labels":"eval"},{"CinGen ID":"CA16020847","Variant Name":"NM_000277.1:c.712A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":23842451,"Raw Comment":"Patient genotype: T238A\/P281L (VarID 589, Pathogenic in ClinVar)","Number of Patients":1,"In trans Variants":["P281L c.(842C>T)"],"labels":"eval"},{"CinGen ID":"CA229781","Variant Name":"NM_000277.2:c.809G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":23856132,"Raw Comment":"Seen in multiple individuals with classic PKU. In homozygous state and in trans with IVS4+5G>T, pretreatment PKU >1200 umol\/L","Number of Patients":"NA","In trans Variants":["IVS4+5G>T"],"labels":"fine-tune"},{"CinGen ID":"CA229559","Variant Name":"NM_000277.2:c.464G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23932990,"Raw Comment":"2 patients: R243Q (P, 8 submitters) \/R155H and V399V (not in ClinVar)\/R155H","Number of Patients":2,"In trans Variants":["p.R243Q c.(728G>A)","p.V399V"],"labels":"fine-tune"},{"CinGen ID":"CA16020951","Variant Name":"NM_000277.3:c.1154T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":23932990,"Raw Comment":"PMID: 23932990 2 Patients are reported to be homozygous for Leu385Pro - 1.0 points","Number of Patients":2,"In trans Variants":["homozygous c.1154T>C p.(Leu385Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA16020786","Variant Name":"NM_001354304.2:c.441+2T>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23932990,"Raw Comment":"[IVS4+2T>A];p.[Y356X]. Phase unknown. PMID: 23932990","Number of Patients":"NA","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229430","Variant Name":"NM_000277.3:c.1315+4A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23932990,"Raw Comment":"This variant was documented in 1 patient with classic PKU with the pathogenic R243Q variant in trans. It was not specified whether parental analysis was performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229431","Variant Name":"NM_000277.3:c.1315+6T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":23932990,"Raw Comment":"This variant was documented in 1 Han Chinese patient patient with mild hyperphenylalaninemia (MHP), and the pathogneic R243Q variant in trans; this variant was also documented in a second Han Chinese patient with mild hyperphenylalaninemia (MHP), and the pathogenic R241C variant in trans. Parental analysis was not performed to confirm compound heterozygosity.","Number of Patients":2,"In trans Variants":["p.R243Q c.(728G>A)","p.R241C c.(721C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020943","Variant Name":"NM_000277.3:c.1118C>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23942198,"Raw Comment":"PMID:23942198 - A373D detected with R158Q, pathogenic in ClinVar, phase unknown - 0.5 points","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA275937","Variant Name":"NM_000277.2:c.242C>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":23942198,"Raw Comment":"Sample D10: p.T81N on allele1 and p.(V230I) on allele 2.","Number of Patients":1,"In trans Variants":["p.(V230I) c.(688G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA916084427","Variant Name":"NM_001354304.2:c.442-1377_509+226del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23942198,"Raw Comment":"It has been previously reported in one patient with PKU (BH4 deficiency excluded by sequencing of the genes in the BH4 cofactor metabolism pathway) (PP4_Moderate) (PMID: 23942198) in presumed trans with the p.A313V variant (Pathogenic per PAH VCEP) (0.5 points; PM3_Supporting).","Number of Patients":1,"In trans Variants":["p.A313V c.(938C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA916084430","Variant Name":"NM_001354304.2:c.510-735_912+434del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":23942198,"Raw Comment":"It has been previously reported in one patient with PKU (BH4 deficiency excluded by sequencing of the genes in the BH4 cofactor metabolism pathway) (PP4_Moderate) (PMID: 23942198) in presumed trans with the p.F55L variant (Pathogenic per PAH VCEP) (0.5 points; PM3_Supporting).","Number of Patients":1,"In trans Variants":["p.F55L c.(163T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229576","Variant Name":"NM_000277.2:c.490A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":23942198,"Raw Comment":"Patient\/Sample 36: PAH variants: I164V and A403V (VarID 92731, Pathogenic)","Number of Patients":1,"In trans Variants":["p.A403V c.(1208C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA253314","Variant Name":"NM_000441.1:c.-103T>C","Condition":"Pendred syndrome","Criterion":"PM3","PMID":23965030,"Raw Comment":"A group of 68 EVA\/Pendred patients with monoallelic SLC26A4 variants screened for KCNJ10 and FOXI1 variants. One individual with a monoallelic c.-103T>C variant identified, but no variants found in KCNJ10 or FOXI1. Likely that this individual was from a different study - not considered for scoring.","Number of Patients":1,"In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":23965030,"Raw Comment":"4 Patients with Pendred syndrome sequenced for SLC26A4 variants as well as FOXI1 and KCNJ10. They found 3 p.Val138Phe homozygotes and 1 compound heterozygote (p.Leu597Ser). Leu597Ser is actually classified as a Benign\/LB variant in ClinVar by 4 labs.","Number of Patients":4,"In trans Variants":["homozygous c.412G>T p.(Val138Phe)","homozygous c.412G>T p.(Val138Phe)","homozygous c.412G>T p.(Val138Phe)","p.Leu597Ser c.(1790T>C)"],"labels":"eval"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":24007330,"Raw Comment":"Identified patients with p.H723R\/p.T410M genotype and found that they had better residual hearing thatn those with homozygous p.H723R genotype. THere is little detail about the patients themselves and therefore it is unclear how many cases they had, but there were 4 alleles of the p.T410M variant","Number of Patients":"NA","In trans Variants":["p.T410M c.(1229C>T)","p.H723R c.(2168A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA8814791","Variant Name":"NM_000152.3:c.118C>T","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":24107549,"Raw Comment":"Report of a family with 10 out of 13 siblings affected by late-onset Pompe disease. Three variants segregated in the family. One sibling, with a progressive undefined myopathy, was deceased. Seven siblings were compound heterozygous for c.118C>T (p.Arg40X) and c.2647-7G>A [p.Asn882fs] (VOUS based on the guidelines of the ClinGen LSD VCEP) in GAA. Of note, two other siblings are compound heterozygous for c.2276G>A (p.Gly759Arg) and c.2647-7G>A, and one unaffected sibling is heterozygous for c.2276G>C. While it is highly likely that the variants are in trans, parental testing results are unavailable. Six siblings with the p.Arg40X\/c.2647-7G>A genotype had muscle GAA activity <10% the lower limit of normal.","Number of Patients":10,"In trans Variants":["c.118C>T p.Arg40X","c.2647-7G>A p.Asn882fs"],"labels":"eval"},{"CinGen ID":"CA172240","Variant Name":"NM_004004.5:c.71G>A","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":24123366,"Raw Comment":"Variant identified as homozygous in one individual with hearing loss.","Number of Patients":1,"In trans Variants":["homozygous c.71G>A p.(Trp24*)"],"labels":"eval"},{"CinGen ID":"CA229621","Variant Name":"NM_000277.3:c.558_559del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":24130151,"Raw Comment":"PMID: 24130151 - W187fs detected in homozygous state, both parents confirmed to be heterozygous (consanguineous) - 0.5 points","Number of Patients":1,"In trans Variants":["homozygous c.558_559del p.(Trp187Glyfs*12)"],"labels":"fine-tune"},{"CinGen ID":"CA8815664","Variant Name":"NM_000152.4:c.2237G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Very Strong","PMID":24158270,"Raw Comment":"Three patients are compound heterozygous for c.2237G>A (p.Trp746Ter) and c.-32-13T>G, a well-known pathogenic variant. The phase of the variants was not confirmed. One out of the threee patients meet PP4 criteria. No points were awarded since the phase was not confirmed and in trans data for c.-32-13T>G has already been counted.","Number of Patients":3,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA172217","Variant Name":"NM_004004.5:c.167del","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":24158611,"Raw Comment":"10 patients and 11 alleles or 2% representing 6% of the mutated alleles, 1 homozygote,variant in EC1 domain, AR, phenotype severity ranging from moderateto 3 profound bialleic or double het with GJB6, the homozygote was profoundly affected,","Number of Patients":10,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA262054","Variant Name":"NM_206933.2:c.1036A>C","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":24160897,"Raw Comment":"detected in trans with p.R1295X","Number of Patients":1,"In trans Variants":["p.R1295X"],"labels":"fine-tune"},{"CinGen ID":"CA253338","Variant Name":"NM_022124.5:c.719C>T","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Strong","PMID":24164807,"Raw Comment":"Identified heterozygous in three affected siblings who also had a heterozygous PCDH15 variant.","Number of Patients":3,"In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA229718","Variant Name":"NM_000277.1:c.724C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":24190797,"Raw Comment":"L242F seen in 1 patient with R158Q (VarID 587, Pathogenic)","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA253312","Variant Name":"NM_000441.1:c.412G>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":24224479,"Raw Comment":"Total: 2 compound het with path variant. Identified two brothers who have Pendred syndrome. Both were positive for the p.Val138Phe and p.Leu445Trp (Path in ClinVar by 4 labs including LMM & GeneDx). Also identified a female patient with Pendred who had the variant in trans with p.Glu384Gly variant (Path\/LP in ClinVar by LMM, GeneDx, Counsyl)","Number of Patients":3,"In trans Variants":["p.Glu384Gly c.(1151A>G)","p.Leu445Trp c.(1334T>G)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":24224479,"Raw Comment":"This paper also identified a case with compound heterozygous mutations p.Thr410Met and p.Tyr530His in SLC26A4. The patient had cochlear dysplaisa, EVA, no Goiter, congenital hypothyroidism, and was an 8 year old male. The p.Tyr530His variant is considered pathogenic.","Number of Patients":1,"In trans Variants":["p.Tyr530His c.(1588T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA402994573","Variant Name":"NM_000156.6:c.497T>C","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":24268530,"Raw Comment":"1 hom patient (PMID: 24268530)","Number of Patients":1,"In trans Variants":["homozygous c.497T>C p.(Leu166Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA8814791","Variant Name":"NM_000152.3:c.118C>T","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":24269976,"Raw Comment":"Patient PD10 is compound heterozygous for c.118C>T (p.Arg40Ter) and c.2815_2816del p.Val939fsX78. The diagnosis was based on clinical presentation and reduced GAA enzyme activity in leukocytes or dried blood spots. The phase of the variants is unknown. This data was not included because specific values for GAA activity were not provided.","Number of Patients":1,"In trans Variants":["c.2815_2816del p.Val939fsX78"],"labels":"fine-tune"},{"CinGen ID":"CA8815664","Variant Name":"NM_000152.4:c.2237G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Very Strong","PMID":24269976,"Raw Comment":"Patient 1 is compound heterozygous for c.2237G>A (p.Trp746Ter) and c.1753G>A (p.Glu579Lys) and patient 9 is compound heterozygous for c.2237G>A (p.Trp746Ter) and c.378G>A (p.Trp126Ter). The phase of the variants was not confirmed. These patients do not meet PP4 criteria and therefore no points were awarded.","Number of Patients":2,"In trans Variants":["c.1753G>A (p.Glu579Lys)","c.378G>A (p.Trp126Ter)"],"labels":"fine-tune"},{"CinGen ID":"CA10602335","Variant Name":"NM_000277.1:c.971T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":24327145,"Raw Comment":"Patient #7 I324N \/ R243Q with moderate PKU (720-780umol\/L Phe)","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":24338212,"Raw Comment":"2 compound het individuals from the same family with the p.H723R\/p.T410M genotype and hearing loss. One had stable HL and the other had fluctuating hearing loss.","Number of Patients":2,"In trans Variants":["p.H723R c.(2168A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA357242","Variant Name":"NM_000277.2:c.110T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":24350308,"Raw Comment":"Patient genotype: p.R408W(c.1222C>T)\/p.L37P(c.110C>T)","Number of Patients":1,"In trans Variants":["p.R408W(c.1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229857","Variant Name":"NM_000277.1:c.935G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":24350308,"Raw Comment":"Single patient reported G312D\/R408W with undefined BH4 responsiveness and classic PKU","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020990","Variant Name":"NM_000277.1:c.1301C>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":24350308,"Raw Comment":"A434V seen with p.R243* in 1 patient (VarID 588, Pathogenic)","Number of Patients":1,"In trans Variants":["p.R243* c.(727C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020949","Variant Name":"NM_000277.2:c.1147C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":24350308,"Raw Comment":"in trans with R408W in a patient with classic PKU","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020760","Variant Name":"NM_001354304.2:c.277_280del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":24350308,"Raw Comment":"detected with pathogenic variant p.R408W (c.1222C>T) parental testing not reported PMID: 24350308","Number of Patients":0,"In trans Variants":["p.R408W (c.1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020898","Variant Name":"NM_001354304.2:c.920G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24350308,"Raw Comment":"2 patients with c.920G>A in trans with pathogenic variants","Number of Patients":"2","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA400024376","Variant Name":"NM_000212.3:c.792G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":24357714,"Raw Comment":"One proband was homozygous for the variant (PMID:24357714). Total points: .5 (PM3_Supporting).\n","Number of Patients":1,"In trans Variants":["homozygous c.792G>A p.(Trp264*)"],"labels":"fine-tune"},{"CinGen ID":"CA251535","Variant Name":"NM_000277.3:c.281_283TCA[1]","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24368688,"Raw Comment":"Documented in 1 PKU patient from New South Wales, Australia, who was a compound heterozygote with the likely pathogenic p.S349P variant in trans. Parental analysis was not performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["p.S349P c.(1045T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA16020795","Variant Name":"NM_000277.3:c.461A>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":24368688,"Raw Comment":"Detected with c.1315+1G>A (IVS12+1G>A) (pathogenic 13 submitters) and p.G103C (VUS) PMID: 24368688","Number of Patients":"NA","In trans Variants":["c.1315+1G>A (IVS12+1G>A)","p.G103C c.(307G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229785","Variant Name":"NM_000277.2:c.818C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24368688,"Raw Comment":"Patient 32 genotype: I65T\/ S273F. Patient 111 genotype: S273F\/ R408W.","Number of Patients":2,"In trans Variants":["p.R408W c.(1222C>T)","p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA286497","Variant Name":"NM_000277.2:c.1033G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":24368688,"Raw Comment":"Seen in an individual with PKU, second allele R408W. Pathogenic in Clinvar (Var ID=577).","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA6748984","Variant Name":"NM_000277.2:c.307G>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":24368688,"Raw Comment":"Table 1. Patient 97. Allele 1: c.307G>T\/ Allele 2: c.461A>T (p.Y154F) Novel.","Number of Patients":1,"In trans Variants":["c.461A>T p.Y154F"],"labels":"fine-tune"},{"CinGen ID":"CA229539","Variant Name":"NM_000277.2:c.434A>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24368688,"Raw Comment":"Patient 8 genotype: p.I65T\/p.D145V","Number of Patients":1,"In trans Variants":["p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229724","Variant Name":"NM_000277.2:c.733G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":24368688,"Raw Comment":"Patient 55: R408Q (VarID 612, Pathogenic), Patient 72: A104D (VarID 102650, Pathogenic)","Number of Patients":2,"In trans Variants":["p.A104D c.(311C>A)","p.R408Q c.(1223G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229452","Variant Name":"NM_000277.2:c.168+1G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":24368688,"Raw Comment":"in trans with c.745C>T","Number of Patients":"NA","In trans Variants":["c.745C>T p.(Leu249Phe)"],"labels":"fine-tune"},{"CinGen ID":"CA229515","Variant Name":"NM_000277.2:c.311C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24368688,"Raw Comment":"ID #72: p.A104D\/p.V245L (VarID 102810, Pathogenic\/ likely pathogenic)","Number of Patients":1,"In trans Variants":["p.V245L c.(733G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA220584","Variant Name":"NM_000277.2:c.500A>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24368688,"Raw Comment":"Patient 7: N167I\/R408W","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA251530","Variant Name":"NM_000277.2:c.473G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":24368688,"Raw Comment":"Patient 5, 38: R158Q\/ c.1315+1G>A (VarID576, Pathogenic). Patient 75: R158Q\/ p.P281L (VarID 589, Pathogenic). Patient 98: R158Q\/ p.R261* (VarID 610, Pathogenic).","Number of Patients":3,"In trans Variants":["p.P281L c.(842C>T)","p.R261* c.(781C>T)","c.1315+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA16020732","Variant Name":"NM_001354304.1:c.168+1G>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":24368688,"Raw Comment":"The second variants included: R111* and the pathogenic L249F.","Number of Patients":"NA","In trans Variants":["p.L249F c.(745C>T)","p.R111* c.(331C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229559","Variant Name":"NM_000277.2:c.464G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24401910,"Raw Comment":"Patient 17 genotype: R111X (P, 7 submitters) + R155H. When sequence alteration was identified, paternal or maternal origin was determined whenever the parental DNA was available.","Number of Patients":1,"In trans Variants":["p.R111X"],"labels":"fine-tune"},{"CinGen ID":"CA229447","Variant Name":"NM_000277.2:c.158G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":24401910,"Raw Comment":"Compound heterozygosity with V388L (LP)","Number of Patients":1,"In trans Variants":["p.V388L c.(1162G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA16020862","Variant Name":"NM_000277.1:c.800A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":24401910,"Raw Comment":"Patient (20) Genotype: G257V (VarID 102830) + Q267R. When sequence alteration was identified, paternal or maternal origin was determined whenever the parental DNA was available.","Number of Patients":1,"In trans Variants":["p.G257V c.(770G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020796","Variant Name":"NM_001354304.2:c.456_463dup","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":24401910,"Raw Comment":"The patient from PMID: 24401910 is compound heterozygous for this frameshift variant and the splice variant c.611A>G (ClinVar 590,Pathogenic), unknown if trans phase was confirmed. 0.5pt","Number of Patients":1,"In trans Variants":["c.611A>G p.(Tyr204Cys)"],"labels":"fine-tune"},{"CinGen ID":"CA220590","Variant Name":"NM_000277.2:c.890G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24401910,"Raw Comment":"Table 2 (31) R413P + R297H (VarID: 592, Pathogenic). When sequence alteration was identified, paternal or maternal origin was determined whenever the parental DNA was available.","Number of Patients":1,"In trans Variants":["p.R413P c.(1238G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA6748732","Variant Name":"NM_000277.3:c.1174T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":24401910,"Raw Comment":"This variant was detected in trans with the pathogenic PAH variant Arg408Gln in 1 patient with mild hyperphenylalaninemia. Parental analysis was not performed to confirm compound heterozygosity. This variant was documented in a 2nd patient diagnosed with mild hyperphenylalaninemia (MHP), however, the variant in trans was not specified.","Number of Patients":2,"In trans Variants":["p.Arg408Gln c.(1223G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA281520","Variant Name":"NM_000277.1:c.-4165_-407del","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24401910,"Raw Comment":"5: \u00e2\u0088\u00924173_\u00e2\u0088\u0092407del+E286K (2 patients). 11:\u00e2\u0088\u00924173_\u00e2\u0088\u0092407del+E76G (likely same patient as Chen 2002). 14:\u00e2\u0088\u00924173_\u00e2\u0088\u0092407del+R408Q (2 patients, likely same patients as Chen 2002).","Number of Patients":5,"In trans Variants":["-4173\\_-407del","-4173\\_-407del+E76G","-4173\\_-407del+E286K","-4173\\_-407del+R408Q"],"labels":"fine-tune"},{"CinGen ID":"CA402996954","Variant Name":"NM_000156.6:c.224C>T","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":24415674,"Raw Comment":"One individual with clinical and biochemical features of GAMT deficiency is homozygous for the variant. (PMID: 24415674), 0.5 points, PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.224C>T p.(Ala75Val)"],"labels":"fine-tune"},{"CinGen ID":"CA402994686","Variant Name":"NM_000156.6:c.476T>C","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":24415674,"Raw Comment":"PMID: 24415674: Identified in one homozygous proband (0.5pts)","Number of Patients":1,"In trans Variants":["homozygous c.476T>C p.(Leu159Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA402997207","Variant Name":"NM_138924.3:c.202G>T","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":24415674,"Raw Comment":"Identified in one homozygous proband (0.5pts) (PMID: 24415674)","Number of Patients":1,"In trans Variants":["homozygous c.202G>T p.(Gly68Cys)"],"labels":"fine-tune"},{"CinGen ID":"CA402997017","Variant Name":"NM_138924.3:c.220G>C","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3","PMID":24415674,"Raw Comment":"Identified in two unrelated individuals with guanidinoacetate methyltransferase deficiency (PMID: 24415674): one was a homozygote for the variant (0.5pts) and the other was a reported compound heterozygote who carried a reported pathogenic variant (c.327G>A, see ClinVar Variation ID: 21065) with unknown phase (0.5pts) (1pt total)","Number of Patients":2,"In trans Variants":["homozygous c.220G>C p.(Ala74Pro)","c.327G>A"],"labels":"fine-tune"},{"CinGen ID":"CA402995088","Variant Name":"NM_138924.3:c.439C>T","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3-Supporting","PMID":24415674,"Raw Comment":"PMID: 24415674: Identified in one individual who was a reported compound heterozygote who carried a pathogenic variant in unknown phase (c.11_36dup (p.Gly13fs), ClinVar Variation ID: 858462, PVS1, PM3_Supporting, PP4_Strong) (0.5pts). ","Number of Patients":1,"In trans Variants":["[\"c.11\\_36dup p.Gly13fs\"]"],"labels":"fine-tune"},{"CinGen ID":"CA8603182","Variant Name":"NM_000419.4:c.1234G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Strong","PMID":24418945,"Raw Comment":"The proband is reported to be compound heterozygous for the Pathogenic variant c.1214T>C (p.Ile405Thr) and c.1234G>A (p.Gly412Arg) however confirmation of the trans phasing is not reported. 0.5 pt","Number of Patients":1,"In trans Variants":["c.1214T>C p.Ile405Thr"],"labels":"fine-tune"},{"CinGen ID":"CA290950815","Variant Name":"NM_000419.4:c.1214T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":24418945,"Raw Comment":"The proband is reported to be compound heterozygous for c.1214T>C (p.Ile405Thr) and Pathogenic variant c.1234G>A (p.Gly412Arg) however confirmation of the trans phasing is not reported. However, to avoid circularity the proband was counted only towards the classification of Gly412Arg not Ile405Thr.","Number of Patients":1,"In trans Variants":["c.1234G>A p.Gly412Arg"],"labels":"fine-tune"},{"CinGen ID":"CA214218","Variant Name":"NM_000536.4:c.217C>T","Condition":"recombinase activating gene 2 deficiency","Criterion":"PM3","PMID":24481607,"Raw Comment":"PMID: 24481607: Proband compound heterozygous (comp het ( R73C\/C178X, Pathogenic according to SCID VCEP specifications, 1 pt, PM3_met).\t","Number of Patients":1,"In trans Variants":["p.C178X"],"labels":"fine-tune"},{"CinGen ID":"CA915949503","Variant Name":"NM_000018.4:c.552del","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Supporting","PMID":24503138,"Raw Comment":"This variant has been detected in at least 1 individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This individual is a compound heterozygous for the variant and a pathogenic variant (p.V283A) although the variants are not confirmed in trans. Based on ACADVL VCEP specific guidelines, a total of 0.5 points is awarded for this criteria. [PMID 24503138]\n","Number of Patients":1,"In trans Variants":["p.V283A c.(848T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA172217","Variant Name":"NM_004004.5:c.167del","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":24529908,"Raw Comment":"76-81% in AJ, cohort Iranian\/Turkish presumed ARNSHL, describe 1 homozygote,","Number of Patients":1,"In trans Variants":["homozygous c.167del p.(Leu56Argfs*26)"],"labels":"fine-tune"},{"CinGen ID":"CA023585","Variant Name":"NM_000527.5:c.1784G>A","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":24585268,"Raw Comment":"Variant meets PM2 and is identified in an index case with homozygous FH phenotype (LDL = 16 mmol\/L) and LDLR variant c.(1705+1_1706-1)_(*2514_?)del (described as 16kb deletion exon 12-18) (PMID: 24585268), classified as Pathogenic by these guidelines, in trans, so PM3 is Met.","Number of Patients":1,"In trans Variants":["c.(1705+1_1706-1)_(*2514_?)del"],"labels":"fine-tune"},{"CinGen ID":"CA253338","Variant Name":"NM_022124.5:c.719C>T","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Strong","PMID":24618850,"Raw Comment":"Patient with Usher syndrome who had a homozygous missense variant in MYO7A and was also heterozygous for Pro240Leu in CDH23","Number of Patients":1,"In trans Variants":["homozygous c.719C>T p.(Pro240Leu)"],"labels":"eval"},{"CinGen ID":"CA229699","Variant Name":"NM_000277.2:c.699C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24705691,"Raw Comment":"Patient 11 Genotype: c.699C>A, F233L (maternally inherited)\/ p.S70del (paternally inherited)","Number of Patients":1,"In trans Variants":["p.S70del"],"labels":"eval"},{"CinGen ID":"CA229789","Variant Name":"NM_000277.2:c.823C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24705691,"Raw Comment":"in trans with c.669delC","Number of Patients":"NA","In trans Variants":["c.669delC p.(Asn223Lysfs*118)"],"labels":"eval"},{"CinGen ID":"CA16020925","Variant Name":"NM_001354304.2:c.1066-13T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":24705691,"Raw Comment":"This variant was documented in a patient in a Chinese cohort with moderate PKU in trans with pathogenic variant p.R243Q. Parental analysis was performed to confirm compound heterozygosity. (PMID 24705691).","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"eval"},{"CinGen ID":"CA274281","Variant Name":"NM_000152.3:c.1548G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":24715333,"Raw Comment":"Patient 11 is compound heterozygous for c.1548G>A (p.Trp516Ter) and c.1913G>T (p.Gly638Val). The phase of the variants is unknown. No residual GAA activity data is available, and therefore this data will not be included for PM3.","Number of Patients":1,"In trans Variants":["c.1913G>T (p.Gly638Val)"],"labels":"eval"},{"CinGen ID":"CA273356","Variant Name":"NM_000277.2:c.745C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":24765287,"Raw Comment":"The diagnosis was confirmed through molecular analysis of the patient as well as the parents. Genetic analysis showed that she is compound heterozygous for the following mutations: p.L249F and p.R261Q (VarID 582, P\/LP). The father carries the first mutation and the mother the second.","Number of Patients":1,"In trans Variants":["p.R261Q c.(782G>A)"],"labels":"eval"},{"CinGen ID":"CA504731701","Variant Name":"NM_138924.3:c.58dup","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3","PMID":24766785,"Raw Comment":"One patient with GAMT deficiency has been reported with this variant. This patient is compound heterozygous for a pathogenic variant, c.327G>A, in trans (PMID 24766785)(1 point)(PM3)","Number of Patients":1,"In trans Variants":["c.327G>A"],"labels":"fine-tune"},{"CinGen ID":"CA262122","Variant Name":"NM_206933.2:c.8559-2A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":24853665,"Raw Comment":"Identified the variant in a homozygous state in an individual with sporadic NSHL.","Number of Patients":1,"In trans Variants":["homozygous c.8559-2A>G "],"labels":"fine-tune"},{"CinGen ID":"CA274024","Variant Name":"NM_000152.4:c.1051delG","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":24923245,"Raw Comment":"This variant was found in 2 patients with c.-32-13T>G. c.-32-13T>G is a well known pathogenic variant. The phase of the variants was not confirmed. These patients do not meet PP4 criteria (control range for GAA activity was not provided). No points were awarded since in trans data for c.-32-13T>G has already been scored and the variants were not confirmed in trans.","Number of Patients":2,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA251522","Variant Name":"NM_000277.2:c.1315+1G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":24941924,"Raw Comment":"In trans with a LOF allele; Table 2 Observed phenotype_Classic PKU","Number of Patients":"1","In trans Variants":["p.LOF"],"labels":"fine-tune"},{"CinGen ID":"CA273111","Variant Name":"NM_000277.1:c.508C>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24941924,"Raw Comment":"c.508C>G\/c.60+5G>T (VarID:102751, Pathogenic); c.508C>G\/c.1315+1G>A (VarID:576, Pathogenic); c.508C>G\/c.842+1G>A (VarID599, P\/LP)","Number of Patients":3,"In trans Variants":["c.842+1G>A","c.1315+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229811","Variant Name":"NM_000277.2:c.842+1G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":24941924,"Raw Comment":"In trans with NM_000277.2(PAH):c.508C>G (p.His170Asp) (Pathogenic in ClinVar)","Number of Patients":1,"In trans Variants":["c.508C>G p.His170Asp"],"labels":"fine-tune"},{"CinGen ID":"CA229845","Variant Name":"NM_000277.2:c.912G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":24941924,"Raw Comment":"Found in the homozygous state in 1 patient. Familial segregation analysis was confirmed in 45 of our patients and in three cases both parents were not available. Carrier state was proved in six of nine homozygous patients\u00e2\u0080\u0099 progenitors; however, in two of the three remaining families, the parents were consanguineous.","Number of Patients":1,"In trans Variants":["homozygous c.912G>A "],"labels":"fine-tune"},{"CinGen ID":"CA16020907","Variant Name":"NM_001354304.2:c.969+6T>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":24941924,"Raw Comment":"One patient has been reported (PMID: 24941924) compound heterozygous for c.969 +6T>C and c.1066\u00e2\u0080\u009011G>A (ClinVar 607 Pathogenic, reviewed by VCEP). Confirmation of trans phase was not reported.","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229482","Variant Name":"NM_000277.2:c.1A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":24941924,"Raw Comment":"It was previously reported in trans with the known pathogenic p.Arg241His allele (PM3) in 1 Mexican proband with mild PKU (PMID: 24941924); BH4 loading test was performed, but exclusion of BH4 deficiency via enzymatic or genetic testing was not performed (PP4)","Number of Patients":1,"In trans Variants":["p.Arg241His c.(722G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229880","Variant Name":"NM_000277.2:c.969+6T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":24941924,"Raw Comment":"detected with c.1162G>A, p.(Val388Met) (VarID619, pathogenic)","Number of Patients":1,"In trans Variants":["c.1162G>A p.Val388Met"],"labels":"fine-tune"},{"CinGen ID":"CA915947736","Variant Name":"NM_000051.4:c.1122_1123del","Condition":"hereditary breast cancer","Criterion":"PM3","PMID":24954719,"Raw Comment":"This variant has been observed in a compound heterozygous state (presumed) in one individual with ataxia-telangiectasia (PMID: 24954719 PM3) (2-POINTS)\n","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA16041896","Variant Name":"NM_000152.5:c.1824_1828dup","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":24976573,"Raw Comment":"A patient with infantile onset Pompe disease and meeting the Clingen LSD VCEP's specifications for PP4 has been described who is homozygous for the variant (PMID 24976573). 0.5 points were given towards PM3. Therefore, PM3_Supporting is met.","Number of Patients":1,"In trans Variants":["homozygous c.1824_1828dup p.(Ala610Aspfs*88)"],"labels":"fine-tune"},{"CinGen ID":"CA16020736","Variant Name":"NM_000277.1:c.176A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":25003100,"Raw Comment":"Patient 8 genotype: D59V\/R261Q (P\/LP in ClinVar)","Number of Patients":1,"In trans Variants":["R261Q c.(782G>A)"],"labels":"eval"},{"CinGen ID":"CA262122","Variant Name":"NM_206933.2:c.8559-2A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":25133613,"Raw Comment":"consanguineous family ARRP04: Identified in a homozygous state in one affected individual. Absent from 30 controls. Cite that this variant is a founder variant in East Asian populations.","Number of Patients":1,"In trans Variants":["homozygous c.8559-2A>G"],"labels":"eval"},{"CinGen ID":"CA143304","Variant Name":"NM_206933.4:c.12874A>G","Condition":"Usher syndrome","Criterion":"PM3-Supporting","PMID":25133751,"Raw Comment":"PMID: 25133751","Number of Patients":"NA","In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA274281","Variant Name":"NM_000152.3:c.1548G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":25243733,"Raw Comment":"Patient 3 is compound heterozygous for c.1548G>A (p.Trp516Ter) and the known pathogenic variant c.2481+1022_646+31del. The variants are in trans based on qRT-PCR analysis. GAA activity in fibroblasts with 4-MU as the substrate was 0.1 nmol 4-MU\/hr\/mg protein (control 122.4). (1 point)","Number of Patients":1,"In trans Variants":["c.2481+1022_646+31del"],"labels":"fine-tune"},{"CinGen ID":"CA400025816","Variant Name":"NM_000212.3:c.1031A>G","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25275492,"Raw Comment":"PMID 25275492 reported this variant in homozygous state in one proband. [0.5 points]","Number of Patients":1,"In trans Variants":["homozygous c.1031A>G p.(Tyr344Cys)"],"labels":"eval"},{"CinGen ID":"CA262105","Variant Name":"NM_206933.2:c.5581G>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":25356976,"Raw Comment":"179 unrelated Chinese patients with inherited retinal dystrophy were tested for variants in 164 known genes. The p.Gly1861Ser variant was identified in 2 patients with Usher syndrome. The patients were compound het for p.G1526R and p.R5143C, respectively. I hesitate to count the patient with the p.R5143C variant in trans because this is the same author that identified that variant in cis in a patient.\n\nNOTE: p.R5143C is benign due to a MAF OF 0.9% in East Asians, and based on Huang 2013, variants likely in cis. Did not count proband with this variant (Andrea)","Number of Patients":2,"In trans Variants":["p.Gly1861Ser c.(5581G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA262122","Variant Name":"NM_206933.2:c.8559-2A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":25356976,"Raw Comment":"This paper identified 2 compound heterozygotes with IRD and 1 homozygote.\nF7-1 (Proband with RP): Variant in trans with a p.T4337M variant in USH2A.\nW176-1 (Proband with Usher syndrome): Homozygous state.\nW272-1 (Proband with Usher syndrome: Variant in trans with c.8917_8918delCT frameshift variant.","Number of Patients":3,"In trans Variants":["p.T4337M c.(13010C>T)","c.8917_8918delCT p.(Leu2973Lysfs*79)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":25372295,"Raw Comment":"Seqeunced 1057 Chinese HL patients. Identified 27 patients with the c.919-2A>G variant in trans with the p.T410M. 8 patients with the genotype: c.2168A.G(p.H723R) c.1229C.T(pT410M). 4 homozygotes. 3 patients with the genotype p.V659L\/p.T410M. Identified 2 cases of the varaint in trans with the p.N392Y variant. Identified 2 patients with the c.1687_1692insA variant in trans with the p.T140M variant. One case in trans with the p.T94I variant. One case in trans with the p.V650D variant. One case in trans with the c.1693insA variant. One patient with the p.S448X variant in trans. One patient with the IVS19+2T>A variant in trans. There were many more variants in trans and 4 cases with wt in trans, but since the PM3 points are maxed, they will not be noted here.","Number of Patients":35,"In trans Variants":["homozygous c.919-2A>G","p.T410M c.(1229C>T)","c.2168A.G p.H723R","p.N392Y c.(1174A>T)","c.1687_1692insA","p.T94I c.(281C>T)","p.V650D c.(1949T>A)","c.1693insA","p.S448X","IVS19+2T>A"],"labels":"eval"},{"CinGen ID":"CA915940324","Variant Name":"NM_000419.5:c.2326_2331dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25373348,"Raw Comment":"GT12 of PMID: 25373348 is compound heterozygous for the maternal c.2326_2331dup variant and Tyr319Ter (classified Pathogenic by the PD-EP). Confirmation of trans phase was not reported. (0.5pt; PM3_supporting)","Number of Patients":1,"In trans Variants":["p.Tyr319Ter c.(957T>G)"],"labels":"fine-tune"},{"CinGen ID":"CA915940323","Variant Name":"NM_000419.5:c.3092del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25373348,"Raw Comment":"GT11 of PMID: 25373348 is compound heterozygous for the maternal c.3092del variant and Leu214Pro (classified Pathogenic by the PD-EP), without confirmation of trans phase (0.5pt; PM3_supporting).","Number of Patients":1,"In trans Variants":["p.Leu214Pro c.(641T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA915940325","Variant Name":"NM_000419.5:c.310+3_310+6del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25373348,"Raw Comment":"GT3 of PMID: 25373348 is homozygous for this variant 0.5pt\t","Number of Patients":1,"In trans Variants":["homozygous c.310+3_310+6del "],"labels":"fine-tune"},{"CinGen ID":"CA291240306","Variant Name":"NM_000212.2:c.31T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":25373348,"Raw Comment":"Patient GT2 has the Trp11Arg variant in trans with Cys486Trp (Likely Pathogenic). Phase is confirmed to be in trans. In order to avoid a circular argument, this in trans variant is not counted toward PM3 for Trp11Arg as Trp11Arg is counted toward Cys486Trp.","Number of Patients":1,"In trans Variants":["p.Cys486Trp c.(1458C>G)"],"labels":"fine-tune"},{"CinGen ID":"CA399805736","Variant Name":"NM_000419.5:c.555T>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25373348,"Raw Comment":"This variant has been observed in combination with the VCEP-curated pathogenic ITGA2B variant c.1882C>T (p.Arg628Ter) in 1 proband (GT13, PMID: 25373348). However, the phase of these two variants was not confirmed. This occurrence with phase unknown scores 0.5 points, meeting PM3 at the downgraded strength level of supporting (PM3_supporting).","Number of Patients":1,"In trans Variants":["c.1882C>T p.Arg628Ter"],"labels":"fine-tune"},{"CinGen ID":"CA291227621","Variant Name":"NM_000212.3:c.1813G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25373348,"Raw Comment":"GT4 of PMID: 25373348 is compound heterozygous for Arg242Gln (classified Pathogenic by the PD-EP) and Gly605Ser. Confirmation of trans phase was not reported (PM3_supporting).","Number of Patients":1,"In trans Variants":["p.Arg242Gln c.(725G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA915940267","Variant Name":"NM_000419.5:c.2374del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25373348,"Raw Comment":"GT1 of PMID: 25373348 is homozygous for c.2374del (parents confirmed carriers). 0.5pt\t","Number of Patients":1,"In trans Variants":["homozygous c.2374del p.(Val792Trpfs*34)"],"labels":"fine-tune"},{"CinGen ID":"CA400029953","Variant Name":"NM_000212.2:c.1594T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":25373348,"Raw Comment":"Patient GT15 has the Cys532Arg variant in trans with the Pathogenic variant c.2014+1G>A. Phase is confirmed to be in trans.","Number of Patients":1,"In trans Variants":["c.2014+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA915940322","Variant Name":"NM_000419.5:c.3091del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":25373348,"Raw Comment":"GT10 of PMID: 25373348 is compound heterozygous for the paternal c.1210+105A>G (classified Likely Pathogenic by the PD-EP) and the maternal c.3091delC variants (1pt; PM3).","Number of Patients":1,"In trans Variants":["c.1210+105A>G"],"labels":"fine-tune"},{"CinGen ID":"CA400029369","Variant Name":"NM_000212.2:c.1458C>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":25373348,"Raw Comment":"Patient GT2 has the Trp11Arg variant (VUS) in trans with Cys486Trp. Phase is confirmed to be in trans.","Number of Patients":1,"In trans Variants":["p.Trp11Arg c.(31T>A)"],"labels":"fine-tune"},{"CinGen ID":"CA348611","Variant Name":"NM_000059.4:c.632-3C>G","Condition":"breast-ovarian cancer, familial, susceptibility to, 2","Criterion":"PM3","PMID":25381700,"Raw Comment":"This variant has been detected in 2 siblings with phenotype consistent with BRCA2-Fanconi Anemia (FA). At least two clinical features of FA (physical features, pathology findings and cancer diagnosis \u00e2\u0089\u00a45yr) and confirmed chromosome breakage, are seen in these individuals. Both siblings were homozygous for the variant. Total points equated to 2 (PM3 met; PMID: 25381700).","Number of Patients":2,"In trans Variants":["homozygous c.632-3C>G "],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":25394566,"Raw Comment":"Identified the varaint in trans with a p.Gly209Val variant (Path by 5 submitters in ClinVar) in one patient and a p.Glu29Gln variant in another patient (P by LMM LP\/P by 2 other labs in ClinVar).","Number of Patients":2,"In trans Variants":["p.Gly209Val c.(626G>T)","p.Glu29Gln c.(85G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA184505","Variant Name":"NM_000260.3:c.3503G>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":25404053,"Raw Comment":"Arg1168Gln was identified in 2 patients with Usher syndrome. RP-807 harbored Arg1168Gln \/ Leu1839Pro (vus). RP-1924 harbored Gln1798X \/ Arg1168Gln. Both patients were reported to have segregation analysis performed in family members.","Number of Patients":2,"In trans Variants":["p.Leu1839Pro c.(5516T>C)","p.Gln1798X"],"labels":"eval"},{"CinGen ID":"CA275277","Variant Name":"NM_206933.2:c.8682-9A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":25425308,"Raw Comment":"1 homozygote and 2 compound hets with rare VUS with Usher syndrome, total of 0.75 points for PM3. The compound hets harbored Leu1673Pro, and I was not sure if they were sibs, so scored lower points under PM3 versus scoring a segregation under PP1.","Number of Patients":3,"In trans Variants":["p.Leu1673Pro c.(5018T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA274024","Variant Name":"NM_000152.4:c.1051delG","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":25455803,"Raw Comment":"This variant was found in patient 9 with c.-32-13T>G. c.-32-13T>G is a well known pathogenic variant. The phase of the variants was not confirmed and the patient does not meet PP4 criteria. Therefore, no points were awarded.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA16608675","Variant Name":"NM_000152.4:c.1478C>T","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":25455803,"Raw Comment":"Patient 14 is a compound heterozygote for c.1478C>T and c.525delT. The phase of the variants was not confirmed. GAA activity in the patient was not specified (0 points).","Number of Patients":1,"In trans Variants":["c.525delT p.(Glu176Argfs*45)"],"labels":"fine-tune"},{"CinGen ID":"CA273892","Variant Name":"NM_000152.3:c.1933G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":25455803,"Raw Comment":"Patient 4, with infantile onset Pompe disease, is compound heterozygous for c.1933G>A (p.Asp645Asn) and c.784G>A (p.Glu262Lys). The phase of the variants is unknown. No residual GAA activity is available and therefore this data will not be included. The patient is on enzyme replacement therapy.","Number of Patients":1,"In trans Variants":"[\"c.784G>A p.Glu262Lys\"]","labels":"fine-tune"},{"CinGen ID":"CA274472","Variant Name":"NM_000152.4:c.1438-1G>C","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":25455803,"Raw Comment":"P18 is compound heterozygous for c.1438-1G>C and c.-32-13T>G (written as c.-45T>G in the article). The phase is unknown. The patient is described as having late-onset Pompe disease but results of GAA enzyme activity were not provided, and therefore this data will not be included (does not meet PP4).","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA229430","Variant Name":"NM_000277.3:c.1315+4A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":25456745,"Raw Comment":"This variant was documented in 1 patient with HPA and the likely pathogenic c.724C>T variant in trans. It was not specified whether parental analysis was performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["c.724C>T p.(Leu242Phe)"],"labels":"fine-tune"},{"CinGen ID":"CA229730","Variant Name":"NM_000277.2:c.739G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":25456745,"Raw Comment":"Patient genotype: G247S + T 200fsX6 (VarID 102748).","Number of Patients":1,"In trans Variants":["G247S+T 200fsX6"],"labels":"fine-tune"},{"CinGen ID":"CA229887","Variant Name":"NM_000277.2:c.977G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":25456745,"Raw Comment":"Single patient with HPA","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229490","Variant Name":"NM_000277.1:c.207_209delTTC","Condition":"phenylketonuria","Criterion":"PM3","PMID":25456745,"Raw Comment":"In trans with:\nc.1045T>G, p.Ser349Ala (not provided, ClinGen)\nc.842+2T>A, p.IVS7+2T>A (P, ClinGen)","Number of Patients":"NA","In trans Variants":["c.842+2T>A","p.IVS7+2T>A","c.1045T>G p.(Ser349Ala)","p.Ser349Ala c.(1045T>G)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":25468468,"Raw Comment":"SLC26A4 p.Thr410Met homozygous mutation in a patient with a cystic\ncochlea and an enlarged vestibular aqueduct showing characteristic\nfeatures of incomplete partition type I and II","Number of Patients":1,"In trans Variants":["homozygous c.1229C>T p.(Thr410Met)"],"labels":"fine-tune"},{"CinGen ID":"CA915940297","Variant Name":"NM_000419.5:c.2637del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":25539746,"Raw Comment":"This variant has been observed in an individual (GT-5, PMID: 25539746) in trans with ITGA2B variant NM_000419.4:c.1612G>T (p.Glu538Ter) classified by the Platelet Disorders VCEP as pathogenic, sufficient to apply PM3.","Number of Patients":1,"In trans Variants":["c.1612G>T (p.Glu538Ter)"],"labels":"eval"},{"CinGen ID":"CA913189248","Variant Name":"NM_000419.4:c.2965del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":25539746,"Raw Comment":"Patient GT-8 is homozygous for the c.2965del frameshift variant. 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.2965del p.(Ala989Profs*?)"],"labels":"eval"},{"CinGen ID":"CA8602816","Variant Name":"NM_000419.4:c.2113T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":25539746,"Raw Comment":"Patient GT-3 is homozygous for Cys705Arg (reported as Cys674Arg).","Number of Patients":1,"In trans Variants":["homozygous c.2113T>C p.(Cys705Arg)"],"labels":"eval"},{"CinGen ID":"CA399806384","Variant Name":"NM_000419.5:c.266G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25539746,"Raw Comment":"This variant has been observed in homozygosity in one individual (GT-13, PMID: 25539746), sufficient to apply PM3_supporting. This variant was reported as p.Trp51Stop (without signal peptide) in the publication, but was determined to be p.Trp58Ter\/p.Trp89Ter through personal communication with the corresponding author, Dr. Jos\u00c3\u00a9 Rivera.","Number of Patients":1,"In trans Variants":["homozygous c.266G>A p.(Trp89*)"],"labels":"eval"},{"CinGen ID":"CA915940788","Variant Name":"NM_000419.5:c.1599_1600del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25539746,"Raw Comment":"This variant has been detected in homozygosity in at least 1 proband with Glanzmann thrombasthenia (GT-10, PMID: 25539746). Total points: 0.5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1599_1600del p.(Ser534Profs*52)"],"labels":"eval"},{"CinGen ID":"CA16608466","Variant Name":"NM_000419.4:c.2944G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":25539746,"Raw Comment":"GT-6 was described to have triple heterozygosity with a paternally inherited nonsense, Glu538Ter, pathogenic variant and both Val982Met and Ala958Thr occurring as de novo variants. However it was asserted that Ala989Thr was a polymorphism and Val982Met is the second variant of interest in this patient. No confirmation was reported that the variants are in trans phase. 0.5pt","Number of Patients":1,"In trans Variants":["p.Glu538Ter c.(1612G>T)"],"labels":"eval"},{"CinGen ID":"CA234050","Variant Name":"NM_000152.4:c.1841C>A","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":25544546,"Raw Comment":"A patient with infantile onset Pompe disease is described who is heterozygous for three variants - c.1814C>A (p.Thr614Lys), c.1856G>A (p.Ser619Asn) (LP in ClinVar), and c.-32-13T>G. The phase is unknown. Of note, c.-32-13T>G has never been previously reported in infantile onset Pompe disease, suggesting that this variant may be in cis with one of the missense changes. GAA activity in dried blood spots was \"suggestive of Pompe disease\" but no specific measurements were provided; therefore this data will not be included.","Number of Patients":1,"In trans Variants":["c.1814C>A p.Thr614Lys","c.1856G>A p.Ser619Asn"],"labels":"fine-tune"},{"CinGen ID":"CA251528","Variant Name":"NM_000277.1:c.782G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":25596310,"Raw Comment":"Table 2_Residual PAH activity and optimal enzymatic working range of PAH proteins_R261Q in trans with L48S or R408W known PATH var; or R261 homo pt also seen in this table with increased Phe level, reduced residual enzyme activity.","Number of Patients":"NA","In trans Variants":["p.L48S c.(143T>C)","p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA274281","Variant Name":"NM_000152.3:c.1548G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":25626711,"Raw Comment":"Patient 11 is homozygous for c.1548G>A (p.Trp516Ter); Patient 16 is compound heterozygous for this variant and c.IVS14\u00e2\u0080\u0089+\u00e2\u0080\u008920A>G (HGVS nomenclature not provided; therefore this data will not be included). These patients had a \"definite diagnosis of classical infantile Pompe disease\" and were treated with enzyme replacement therapy.","Number of Patients":"err","In trans Variants":["homozygous c.1548G>A p.Trp516Ter"],"labels":"fine-tune"},{"CinGen ID":"CA026270","Variant Name":"NM_000059.4:c.9699_9702del","Condition":"breast-ovarian cancer, familial, susceptibility to, 2","Criterion":"PM3","PMID":25639900,"Raw Comment":"This variant has been detected in 1 individual with phenotype consistent with BRCA2-Fanconi Anemia (FA). At least one clinical feature of FA (physical features, pathology findings and cancer diagnosis \u00e2\u0089\u00a45yr) and confirmed chromosome breakage, is seen in this individual. The individual was compound heterozygous for the variant and a pathogenic or likely pathogenic variant confirmed to be in trans. BRCA2:c.9699_9702del has also been detected in multiple individuals with phenotypic features consistent with FA but who did not meet our criteria for applying PM3. Total points equated to 2 (PM3 met; Ambry and Invitae internal contributors, PMID: 25639900). \n","Number of Patients":1,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA143283","Variant Name":"NM_206933.3:c.12295-3T>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":25649381,"Raw Comment":"European male (35 yo) with nyctalopia, RP, and Group 3 audiology but no subjective hearing loss --> 0 points (phase unknown) - other variant is c.2299delG (p.Glu767Serfs*21) \n\nEuropean male (50 yo) with nyctalopia, RP, and Group 2 audiology but no subjective hearing loss --> 0.5 points (phase unknown) - other variant is c.2299delG (p.Glu767Serfs*21) \n\nEuropean male (54 yo) with nyctalopia and Group 1B audiology but no subjective hearing loss --> 0 points - other variant is c.12093C>A (p.Tyr4031*)","Number of Patients":3,"In trans Variants":["c.2299delG (p.Glu767Serfs*21)","c.2299delG (p.Glu767Serfs*21)","c.12093C>A (p.Tyr4031*)"],"labels":"eval"},{"CinGen ID":"CA399805011","Variant Name":"NM_000419.5:c.857T>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"The p.Val286Asp variant has been reported in homozygous state in one proband by PMID:25728920 [0.5 points]","Number of Patients":1,"In trans Variants":["homozygous c.857T>A p.(Val286Asp)"],"labels":"fine-tune"},{"CinGen ID":"CA626121071","Variant Name":"NM_000419.5:c.1946+3G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"The c.1946+3G>T variant on ITGA2B is present in compound heterozygous state with another splice donor variant c.574+1G>A , which has been previously classified as pathogenic by the PD-VCEP. (0.5 points)\nThis variant was also reported in compound heterozygosity with a missense variant, p.Ile518Asn, in an unrelated individual (GT34). PMID:25728920. This evidence is not considered here to avoid circularity. ","Number of Patients":1,"In trans Variants":["c.574+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA8622892","Variant Name":"NM_000212.2:c.187C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"In patient GT7 the Arg169Ter variant was reported in trans with c.187C>T p.Arg63Cys but the phase was not confirmed. 0.5pt","Number of Patients":1,"In trans Variants":["p.Arg169Ter c.(505C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA8622899","Variant Name":"NM_000212.2:c.224del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":25728920,"Raw Comment":"Patient GT61 is homozygous for c.224del.","Number of Patients":1,"In trans Variants":["homozygous c.224del p.(Cys75Leufs*10)"],"labels":"fine-tune"},{"CinGen ID":"CA915940530","Variant Name":"NM_000419.5:c.*165T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"GT75 is homozygous for the c.*165T>C variant (PMID: 25728920; PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.*165T>C "],"labels":"fine-tune"},{"CinGen ID":"CA400020703","Variant Name":"NM_000212.3:c.262C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"PM3_Supporting is applied for 1 compound heterozygous proband from PMID: 25728920. Variant not confirmed in trans, Leu705CysfsTer4, is classified as pathogenic by the Platelet Disorders VCEP.","Number of Patients":1,"In trans Variants":["p.Leu705CysfsTer4"],"labels":"fine-tune"},{"CinGen ID":"CA915940312","Variant Name":"NM_000419.5:c.2095-19T>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"GT15 (PMID: 25728920) is compound heterozygous for Gln924Ter (classified Pathogenic by the PD-EP) and c.2095-19T>A, confirmation of trans phase was not reported (0.5pt; PM3_supporting)","Number of Patients":1,"In trans Variants":["p.Gln924Ter c.(2770C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA915940309","Variant Name":"NM_000212.3:c.613_614+2del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"This variant occurs in homozygous state in one proband. (PMID:25728920) 0.5 points","Number of Patients":1,"In trans Variants":["homozygous c.613_614+2del "],"labels":"fine-tune"},{"CinGen ID":"CA915940304","Variant Name":"NM_000419.5:c.2148dup","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"The patient GT42 has been reported to be homozygous for p.Leu717fs*3 PMID:25728920","Number of Patients":1,"In trans Variants":["homozygous c.2148dup p.(Leu717Alafs*3)"],"labels":"fine-tune"},{"CinGen ID":"CA399787972","Variant Name":"NM_000419.5:c.3061-1G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"GT31 (PMID: 25728920) is compound heterozygous for c.1771dup (classified Pathogenic by the PD-EP) and c.3061-1G>A. Confirmation of trans phase was not reported. (0.5pt; PM3_supporting)\t","Number of Patients":1,"In trans Variants":["c.1771dup p.(Asp591Glyfs*47)"],"labels":"fine-tune"},{"CinGen ID":"CA399805612","Variant Name":"NM_000419.5:c.601G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":25728920,"Raw Comment":"The p.Gly201Ser variant has been reported in homozygous state in two unrelated individuals by PMID: 25728920 [0.5+0.5 = 1 point] ; PM3 applied.","Number of Patients":2,"In trans Variants":["homozygous c.601G>A p.(Gly201Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA399795351","Variant Name":"NM_000419.5:c.2468G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"This variant has been observed in a proband harboring a second VCEP-classified pathogenic variant (c.1413C>G, p.Tyr471Ter), however the phase of the variants was unconfirmed (PMID: 25728920).","Number of Patients":1,"In trans Variants":["c.1413C>G p.(Tyr471*)"],"labels":"fine-tune"},{"CinGen ID":"CA399796017","Variant Name":"NM_000419.5:c.2421G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"This variant was reported to occur in homozygous state in one proband. (PMID:25728920) 0.5 points","Number of Patients":1,"In trans Variants":["homozygous c.2421G>A p.(Trp807*)"],"labels":"fine-tune"},{"CinGen ID":"CA399802411","Variant Name":"NM_000419.5:c.1618C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"PMID: 25728920 Patient GT67 is compound heterozygous for c.1440-13_1440-1del (classified as pathogenic by the Platelet Disorders VCEP) and Gln540Ter. Confirmation of trans phase was not reported. 0.5pt","Number of Patients":1,"In trans Variants":["c.1440-13_1440-1del"],"labels":"fine-tune"},{"CinGen ID":"CA400025612","Variant Name":"NM_000212.3:c.940G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"PMID: 25728920 reported this variant to be homozygous in one proband. (0.5 points) Therefore, PM3 is applied at supporting strength.","Number of Patients":1,"In trans Variants":["homozygous c.940G>T p.(Asp314Tyr)"],"labels":"fine-tune"},{"CinGen ID":"CA400032825","Variant Name":"NM_000212.3:c.1913+1G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"PMID: 25728920 reports this variant to be homozygous in one proband (GT1). (0.5 points)","Number of Patients":1,"In trans Variants":["homozygous c.1913+1G>A "],"labels":"fine-tune"},{"CinGen ID":"CA399803529","Variant Name":"NM_000419.5:c.1357C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"p.Arg453Ter variant was reported to occur in homozygous state in one proband. (PMID:25728920) 0.5 points","Number of Patients":1,"In trans Variants":["homozygous c.1357C>T p.(Arg453*)"],"labels":"fine-tune"},{"CinGen ID":"CA400025814","Variant Name":"NM_000212.3:c.1031A>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"This variant has been reported to occur in homozygous state in one proband by PMID: 25728920. [0.5 points].","Number of Patients":1,"In trans Variants":["homozygous c.1031A>C p.(Tyr344Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA400025605","Variant Name":"NM_000212.3:c.940-2A>G","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"GT38 of PMID: 25728920 is compound heterozygous for two splice site variants: c.79+1G>A (classified Pathogenic by the PD-EP) and c.940-2A>G. Confirmation of trans phase was not reported. 0.5pt","Number of Patients":1,"In trans Variants":["c.79+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA8602816","Variant Name":"NM_000419.4:c.2113T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":25728920,"Raw Comment":"GT49 is compound heterozygous for c.1440-13_1440-1del and Cys705Arg. Phase not confirmed. This Cys705Arg variant is used in the assessment of c.1440-13_1440-1del so will not be used here to avoid a circular argument.","Number of Patients":1,"In trans Variants":["c.1440-13_1440-1del"],"labels":"fine-tune"},{"CinGen ID":"CA399805506","Variant Name":"NM_000419.5:c.647C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"The p.Ala216Val variant has been reported to occur in homozygosity in one proband (PMID:25728920) 0.5 points.","Number of Patients":1,"In trans Variants":["homozygous c.647C>T p.(Ala216Val)"],"labels":"fine-tune"},{"CinGen ID":"CA399790180","Variant Name":"NM_000419.4:c.2951C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"One homozygous individual, patient GT72, has been reported with the Thr984Lys variant.","Number of Patients":1,"In trans Variants":["p.Thr984Lys c.(2951C>A)"],"labels":"fine-tune"},{"CinGen ID":"CA8602531","Variant Name":"NM_000419.4:c.2915dup","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":25728920,"Raw Comment":"2 compound heterozygous siblings are reported with the pathogenic Ala31ProfsTer2 variant in trans, with phase confirmation. 1 pt","Number of Patients":2,"In trans Variants":["p.Ala31ProfsTer2"],"labels":"fine-tune"},{"CinGen ID":"CA399791171","Variant Name":"NM_000419.5:c.2864T>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"This variant has been observed once in a compound heterozygote (GT21) with c.1440-13_1440-1del (previously classified as Pathogenic by the ClinGen Platelet Disorders VCEP), without trans phase confirmation.","Number of Patients":1,"In trans Variants":["c.1440-13_1440-1del"],"labels":"fine-tune"},{"CinGen ID":"CA115839","Variant Name":"NM_000419.4:c.1073G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":25728920,"Raw Comment":"Patient GT26 is homozygous Arg358His as a result of consanguinity.","Number of Patients":1,"In trans Variants":["homozygous c.1073G>A p.(Arg358His)"],"labels":"fine-tune"},{"CinGen ID":"CA291240306","Variant Name":"NM_000212.2:c.31T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":25728920,"Raw Comment":"Patient GT62 is homozygous for Trp11Arg, family is reported as not consanguineous.","Number of Patients":1,"In trans Variants":["homozygous c.31T>C p.(Trp11Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA290947484","Variant Name":"NM_000419.5:c.2348+5G>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"This variant has been observed in homozygosity in one individual (GT8, PMID: 25728920), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2348+5G>C "],"labels":"fine-tune"},{"CinGen ID":"CA290950815","Variant Name":"NM_000419.4:c.1214T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Strong","PMID":25728920,"Raw Comment":"Patient GT74 is compound heterozygous for c.1214T>C (p.Ile405Thr) and Pathogenic variant c.1440-13_1440-1del, however confirmation of the trans phasing is not reported. However, to avoid circularity the proband was counted only towards the classification of c.1440-13_1440-1del not Ile405Thr.","Number of Patients":1,"In trans Variants":["c.1440-13_1440-1del"],"labels":"fine-tune"},{"CinGen ID":"CA291224511","Variant Name":"NM_000212.3:c.353T>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"p.Leu118His has been reported in triple heterozygosity with two other variants, one a missense variant p.Asp578Asn and the other a frameshift variant p.Ser237CysfsTer13. The p.Asp578Asn and p.Ser237CysfsTer13 variants have be confirmed to be in cis (occurring on the same allele) by sequencing and HRM analysis of the patient's daughter. However, no information about the phase of this particular variant is available. (PMID: 25728920.) The p.Ser237CysfsTer13 has been classified as Pathogenic by ClinGen Platelet VCEP. Since this variant, p.Leu118His, occurs with a Pathogenic variant (phase unconfirmed), PM3_Supporting criteria is met as per GT rule specifications (0.5 points).","Number of Patients":1,"In trans Variants":["p.Ser237CysfsTer13","p.Asp578Asn c.(1732G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA290956162","Variant Name":"NM_000419.4:c.257T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":25728920,"Raw Comment":"Proband GT64 is compound heterozygous for this variant and the c.1440-13_1440-1del variant, which is classified as pathogenic by the Platelet Disorders VCEP. Since phase is not confirmed in this proband, 0.5 pts is applied towards PM3 scoring.","Number of Patients":1,"In trans Variants":["c.1440-13_1440-1del"],"labels":"fine-tune"},{"CinGen ID":"CA399806022","Variant Name":"NM_000419.5:c.423G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":25728920,"Raw Comment":"GT14 of PMID: 25728920 is compound heterozygous for Trp141Cys and c.2902del (classified as Pathogenic by the PD-EP), confirmation of trans phase was not reported (0.5pt; PM3_supporting).","Number of Patients":1,"In trans Variants":["c.2902del p.(Tyr968Metfs*?)"],"labels":"fine-tune"},{"CinGen ID":"CA229679","Variant Name":"NM_000277.1:c.665A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":25757997,"Raw Comment":"Subject 8 had mild PKU and genotype L48S\/D222G","Number of Patients":1,"In trans Variants":["p.L48S c.(143T>C) "],"labels":"eval"},{"CinGen ID":"CA397723872","Variant Name":"NM_001270448.2:c.649C>T","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Supporting","PMID":25834949,"Raw Comment":"This variant has been co-detected with a p.Gly441Asp pathogenic variant in an individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency with unknown phase confirmation (PM3 point 0.5, PM3_Supporting, PMIDs: 25834949). ","Number of Patients":1,"In trans Variants":["p.Gly441Asp"],"labels":"fine-tune"},{"CinGen ID":"CA397723375","Variant Name":"NM_001270448.2:c.415T>C","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Supporting","PMID":25834949,"Raw Comment":"The variant is detected in at least one patient in homozygous fashion (PM3 point 0.5, PM3_Supporting, PMID: 25834949). ","Number of Patients":1,"In trans Variants":["homozygous c.415T>C p.(Cys139Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA8338049","Variant Name":"NM_000018.4:c.1269+1G>A","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Supporting","PMID":25834949,"Raw Comment":"Patient 2 in PMID 25834949 is homozygous for the variant. ","Number of Patients":1,"In trans Variants":["homozygous c.1269+1G>A "],"labels":"fine-tune"},{"CinGen ID":"CA229795","Variant Name":"NM_000277.2:c.827T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":25894915,"Raw Comment":"single patient in trans with I95del (pathogenic in clinvar)","Number of Patients":1,"In trans Variants":["p.I95del"],"labels":"fine-tune"},{"CinGen ID":"CA16020844","Variant Name":"NM_000277.3:c.699C>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":25894915,"Raw Comment":"c.699C>G seen with R243Q (VarID 591, pathogenic) in 1 patient","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229855","Variant Name":"NM_000277.1:c.929C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":25894915,"Raw Comment":"31 unrelated patients and their parents. BH4 defect excluded in all patients. Single patient c.929C>T \/ C.721C>T (pathogenic in ClinVar) with moderate PKU (level at dx=1102umol\/L) with predicted BH4 responsiveness.","Number of Patients":1,"In trans Variants":["c.721C>T p.(Arg241Cys)"],"labels":"fine-tune"},{"CinGen ID":"CA251535","Variant Name":"NM_000277.3:c.281_283TCA[1]","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":25894915,"Raw Comment":"This variant was documented in a Chinese patient from Jiangsu province diagnosed with mild hyperphenylalaninemia (MHP) who was a compound heterozygote with the likely pathogenic M276K variant in trans (PMID: 25894915). In this paper, the variant is referred to as \u00e2\u0080\u0098c.284_286delTCA\u00e2\u0080\u0099, which is the same as the \u00e2\u0080\u0098c.281_283delTCA\u00e2\u0080\u0099 variant. Parental analysis was performed to confirm heterozygosity.","Number of Patients":1,"In trans Variants":["p.M276K c.(827T>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229546","Variant Name":"NM_000277.3:c.441+3G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":25894915,"Raw Comment":"This variant was documented in one Chinese patient with mild PKU, with the pathogenic c.721C>T (p.R241C) variant in trans (PMID: 14321076). Parental analysis was performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["c.721C>T p.R241C"],"labels":"fine-tune"},{"CinGen ID":"CA357240","Variant Name":"NM_000277.2:c.1172G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":25894915,"Raw Comment":"Seen in trans in an individual with MHP in trans with V399V (pathogenic in database)","Number of Patients":1,"In trans Variants":["p.V399V"],"labels":"fine-tune"},{"CinGen ID":"CA273107","Variant Name":"NM_000277.2:c.1068C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":25894915,"Raw Comment":"Identified in several patients in this cohort in trans with p.W326X (Pathogenic), p.R158W, p.G257V, and IVS4-1G>A (Pathogenic).","Number of Patients":"NA","In trans Variants":["p.W326X","IVS4-1G>A","p.G257V c.(770G>T)","p.R158W c.(472C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA143283","Variant Name":"NM_206933.3:c.12295-3T>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":25910913,"Raw Comment":"Proband with retinitis pigmentosa, no HL reported (onset 36 yo) - 0 points","Number of Patients":1,"In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA376065726","Variant Name":"NM_001033855.3:c.82G>C","Condition":"severe combined immunodeficiency due to DCLRE1C deficiency","Criterion":"PM3-Supporting","PMID":25917813,"Raw Comment":"PMID: 25917813: This patient is homozygous, 0.5pts. PM3_Supporting.\t","Number of Patients":1,"In trans Variants":["homozygous c.82G>C p.(Ala28Pro)"],"labels":"eval"},{"CinGen ID":"CA203404964","Variant Name":"NM_001033855.3:c.95C>T","Condition":"severe combined immunodeficiency due to DCLRE1C deficiency","Criterion":"PM3","PMID":25917813,"Raw Comment":"Proband is compound heterozygous, in trans, for del Ex1-3 (at least LP according to our SCID VCEP specifications;) 1 point, PM3_Moderate. (PMID: 25917813).","Number of Patients":1,"In trans Variants":["del Ex1-3"],"labels":"eval"},{"CinGen ID":"CA10584832","Variant Name":"NM_000527.5:c.298G>A","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":25936346,"Raw Comment":"Variant meets PM2 and is identified in an index case with homozygous FH phenotype (LDL-C=10.25 mmol\/L ) as homozygous status, from PMID: 25936346.\n","Number of Patients":1,"In trans Variants":["homozygous c.298G>A p.(Asp100Asn)"],"labels":"fine-tune"},{"CinGen ID":"CA253338","Variant Name":"NM_022124.5:c.719C>T","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Strong","PMID":25963016,"Raw Comment":"Pro240Leu Identified in 7 homozygotes and 7 cmp hets. All patients had hearing loss. Fundoscopy performed in 4 probands and was normal. Normal motor milestones. Was not sure if some of these individuals with same variants were related. Also, there is overlap with Wagatsuma 2007. Cmp hets scored conservatively at 1 point. \np.P240L \/ p.R2029W (VUS, 0.017% in EA);\np.P240L \/ p.R2029W;\np.P240L \/ p.E956K;\np.P240L \/ p.E956K;\np.P240L \/ p.E956K;\np.P240L \/ p.E956K;\np.P240L \/ c.6712 + 1G > A;\np.P240L \/ c.6712 + 1G > A;","Number of Patients":14,"In trans Variants":["p.R2029W c.(6085C>T)","p.E956K c.(2866G>A)","p.E956K c.(2866G>A)","p.E956K c.(2866G>A)","p.E956K c.(2866G>A)","p.E956K c.(2866G>A)","p.E956K c.(2866G>A)","c.6712+1G>A","c.6712+1G>A"],"labels":"eval"},{"CinGen ID":"CA5417032","Variant Name":"NM_001033855.3:c.109+1G>T","Condition":"severe combined immunodeficiency due to DCLRE1C deficiency","Criterion":"PM3","PMID":25981738,"Raw Comment":"Patient 6, PMID: 25981738 is compoud het. with 82kb hemizygous deletion involving exons 1\u00e2\u0080\u00934 of DCLRE1C, alt least LP according to SCID VCEP. 1 point, PM3 is met.","Number of Patients":1,"In trans Variants":["82kb hemizygous deletion involving exons 1\u20134 of DCLRE1C"],"labels":"eval"},{"CinGen ID":"CA132738","Variant Name":"NM_000441.1:c.706C>G","Condition":"Pendred syndrome","Criterion":"PM3-Strong","PMID":25991456,"Raw Comment":"No other pathogenic variant identified in patient. Patient had bilateral SNHL w\/ \u00e2\u0080\u009catypical phenotype\"","Number of Patients":1,"In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA253314","Variant Name":"NM_000441.1:c.-103T>C","Condition":"Pendred syndrome","Criterion":"PM3","PMID":25991456,"Raw Comment":"One proband with bilateral Mondini malformation identified with the c.-103T>C variant and a p.Thr416Pro variant. Phase is not known. A second proband with unilateral auditory nerve hypoplasia, cystic vestibulocochlear anomaly and HL was identified with the c.-103T>C variant and no second variant identified.","Number of Patients":2,"In trans Variants":["p.Thr416Pro c.(1246A>C)"],"labels":"eval"},{"CinGen ID":"CA172208","Variant Name":"NM_004004.5:c.107T>C","Condition":"nonsyndromic genetic deafness","Criterion":"PM3","PMID":26043044,"Raw Comment":"The p.Leu36Pro variant was found in trans with a c.79G>A (p.Val27Ile) and a c.341A>G (p.Glu114Gly) variant, in a Han Chinese hearing loss patient. Both variants found in trans are at high frequency in gnomAD and have been repeatedly reported as Benign in ClinVar.","Number of Patients":1,"In trans Variants":["c.79G>A (p.Val27Ile)","c.341A>G (p.Glu114Gly)"],"labels":"eval"},{"CinGen ID":"CA399803781","Variant Name":"NM_000419.5:c.1233C>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":26096001,"Raw Comment":"This variant has been observed in homozygosity in one individual (Patient C, PMID: 26096001), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1233C>A p.(Tyr411*)"],"labels":"eval"},{"CinGen ID":"CA915940296","Variant Name":"NM_000419.5:c.1608del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":26096001,"Raw Comment":"This variant has been observed in homozygosity in one individual (Patient F, PMID: 26096001), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1608del p.(Asn536Lysfs*29)"],"labels":"eval"},{"CinGen ID":"CA400033218","Variant Name":"NM_000212.3:c.2080C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":26096001,"Raw Comment":"This variant has been observed in homozygosity in one individual (Patient O, PMID: 26096001), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2080C>T p.(Gln694*)"],"labels":"eval"},{"CinGen ID":"CA915940787","Variant Name":"NM_000419.5:c.1460_1461insAGGT","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":26096001,"Raw Comment":"This variant has been observed in homozygosity in one individual (Patient E, PMID: 26096001), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1460_1461insAGGT p.(Ser488Glyfs*100)"],"labels":"eval"},{"CinGen ID":"CA399805518","Variant Name":"NM_000419.5:c.641T>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":26096001,"Raw Comment":"This variant was observed in homozygosity in one individual (Patient B in PMID: 26096001), earning 0.5 points and sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.641T>G p.(Leu214Arg)"],"labels":"eval"},{"CinGen ID":"CA400023704","Variant Name":"NM_000212.3:c.774T>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":26096001,"Raw Comment":"This variant has been observed in homozygosity in one individual (Patient N, PMID: 26096001), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.774T>A p.(Cys258*)"],"labels":"eval"},{"CinGen ID":"CA399805991","Variant Name":"NM_000419.5:c.435C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":26096001,"Raw Comment":"This variant has been observed in combination with a second VCEP-classified pathogenic ITGA2B variant (c.531T>A, p.Cys177Ter) without confirmation of variant phase (PMID: 26096001, Patient A). This occurrence earns 0.5 points and meets the VCEP-established criteria for PM3_supporting.","Number of Patients":1,"In trans Variants":["c.531T>A (p.Cys177Ter)"],"labels":"eval"},{"CinGen ID":"CA172217","Variant Name":"NM_004004.5:c.167del","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":26096904,"Raw Comment":"observed 2.2% frequency (Sicilian) or 3 alleles, 3 cpd het with 35delG (severe-profound) and authors conclude patients haveless severe HL in c.35delG\/truncating alteration compound heterozygotes compared to that in the c.35delG homozygotes.","Number of Patients":"3","In trans Variants":["35delG"],"labels":"fine-tune"},{"CinGen ID":"CA229559","Variant Name":"NM_000277.2:c.464G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26210745,"Raw Comment":"Patient genotype: IVS4+5G>T c.441+5G>T (P\/LP, 8 submitters)\/p.R155H c.464G>A","Number of Patients":1,"In trans Variants":["IVS4+5G>T c.441+5G>T"],"labels":"fine-tune"},{"CinGen ID":"CA409120740","Variant Name":"NM_000022.4:c.603C>G","Condition":"adenosine deaminase deficiency","Criterion":"PM3","PMID":26255240,"Raw Comment":"Patient # 46 was found to be heterozygous for c.603C>G (p.Tyr201*) and c.632G>A (p.Arg211His) which is classified as pathogenic for SCID by the ClinGen SCID VCEP (1 pt.) (PMID: 26255240, PM3)\n","Number of Patients":1,"In trans Variants":["c.632G>A p.Arg211His"],"labels":"fine-tune"},{"CinGen ID":"CA252008","Variant Name":"NM_000022.4:c.646G>A","Condition":"adenosine deaminase deficiency","Criterion":"PM3-Strong","PMID":26255240,"Raw Comment":"This variant has been detected in 15 individuals with ADA deficient SCID. Of those individuals, 3 were compound heterozygous for the variant and a pathogenic variant (Glu319Glyfs*320 ,confirmed in trans ,1pt). 12 individuals were homozygous for the variant (1 pt) (total: 2 pts; PM3_Strong ,PMID : 26255240). ","Number of Patients":15,"In trans Variants":["Glu319Glyfs*320","homozygous c.646G>A p.(Gly216Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA253338","Variant Name":"NM_022124.5:c.719C>T","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Strong","PMID":26264712,"Raw Comment":"4 Korean children with profound hearing loss. 2 homozygotes, 2 compound hets. \nCompound hets: \n- Patient SH59-133 : p.P240L \/ p.T1618K (VUS) (linkage performed, but phase does not appear to be confirmed for variants)\n- Patient SB56-103: c.C719T; c.8574delC p.P240L;p.Asp2858GlufsX8 phase not confirmed\n\n1.75 points (1 from homozygotes, 0.75 from cmp hets)","Number of Patients":4,"In trans Variants":["p.T1618K c.(4853C>A)","c.8574delC p.Asp2858GlufsX8"],"labels":"eval"},{"CinGen ID":"CA262105","Variant Name":"NM_206933.2:c.5581G>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":26310143,"Raw Comment":"This is a case report of a Chinese family with pseudo-dominant Usher syndrome. The proband is compound het for p.Gly1861Ser and p.C934W. There is also an affected brother who has this genotype.","Number of Patients":1,"In trans Variants":["p.C934W c.(2802T>G)"],"labels":"eval"},{"CinGen ID":"CA306130937","Variant Name":"NM_000215.4:c.1837C>T","Condition":"T-B+ severe combined immunodeficiency due to JAK3 deficiency","Criterion":"PM3-Supporting","PMID":26321643,"Raw Comment":"This variant has been detected in at least one individual with SCID, which is homozygous for the variant (0.5 pt) (PM3_Supporting. PMID: 26321643).","Number of Patients":1,"In trans Variants":["homozygous c.1837C>T p.(Arg613*)"],"labels":"fine-tune"},{"CinGen ID":"CA16020810","Variant Name":"NM_000277.2:c.523C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"Patient genotype: c.[523C>T ];[1238G>C], p.[P175S];[R413P]. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.","Number of Patients":1,"In trans Variants":["c.1238G>C,p.R413P"],"labels":"others"},{"CinGen ID":"CA229562","Variant Name":"NM_000277.1:c.466G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26322415,"Raw Comment":"PMID 26322415: listed p.[A156P];[H220P] in one patient with classic PKU (Phe levels >20mg\/dl). All patients fulfilled the diagnostic criteria of PKU, with a blood phenylalanine concentration >2mg\/dl. BH4 deficiency was excluded byanalysis of urinary pterins and dihydropteridine reductase activity in erythrocytes.","Number of Patients":1,"In trans Variants":["p.A156P c.(466G>C)","p.H220P c.(659A>C)"],"labels":"others"},{"CinGen ID":"CA229543","Variant Name":"NM_000277.2:c.440C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26322415,"Raw Comment":"Patient genotype: c.[440C>T ];[1215_1219delAATAC], p.[P147L];[I406Sfs*17]. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.","Number of Patients":1,"In trans Variants":["c.1215_1219delAATAC (p.I406Sfs*17)"],"labels":"others"},{"CinGen ID":"CA10602335","Variant Name":"NM_000277.1:c.971T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26322415,"Raw Comment":"Single patient with this allele c.971T>A \/ c.331C>T (R111*) pathogenic with \"classic PKU\", but no specific Phe levels listed.","Number of Patients":1,"In trans Variants":["c.331C>T p.(R111*)"],"labels":"others"},{"CinGen ID":"CA229753","Variant Name":"NM_000277.2:c.770G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26322415,"Raw Comment":"Genotype: c.[206_208delCTT];[770G>T]\/ p.[P69_S70delinsP];[G257V]\nGenotype 2: c.[1223G>A];[770G>T]\/ p.[R408Q] (VarID 612, Pathogenic);[G257V]","Number of Patients":2,"In trans Variants":["c.206_208delCTT p.P69_S70delinsP","c.1223G>A p.R408Q"],"labels":"others"},{"CinGen ID":"CA229447","Variant Name":"NM_000277.2:c.158G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"Patient genotype: c.[158G>A];[728G>A],p.[R53H];[R243Q]. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.","Number of Patients":1,"In trans Variants":["c.728G>A p.(R243Q)"],"labels":"others"},{"CinGen ID":"CA251539","Variant Name":"NM_000277.2:c.143T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"Patient genotype: c.[143T>C];[739G>C], p.[L48S];[G247R] (LP, 2 submitters). All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.","Number of Patients":1,"In trans Variants":["c.739G>C p.(G247R)"],"labels":"others"},{"CinGen ID":"CA16020715","Variant Name":"NM_000277.1:c.30dup","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26322415,"Raw Comment":"The variant has been previously reported in trans with the known pathogenic p.R243Q allele (PM3) in 1 Chinese case with classic PKU (PMID: 26322415), as assessed by plasma Phe levels; BH4 deficiency was excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes (PP4_Moderate).","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"others"},{"CinGen ID":"CA16020859","Variant Name":"NM_000277.3:c.795C>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"The PAH variant NM_001354304.2:c.795C>A (p.Cys265Ter) was detected in a Chinese patient with mild PKU (mPKU, Phe levels 10\u00e2\u0080\u009320 mg\/dl). The patient was a compound heterozygote with the pathogenic variant NM_000277.3(PAH):c.782G>A (p.Arg261Gln) (ClinVar ID: 582). All patients fulfilled the diagnostic criteria of PKU, with a blood phenylalanine concentration >2 mg\/dl. BH4 deficiency was excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes. All mutations identified in patients were confirmed by analyzing parental DNA. (PMID: 26322415)\nPM3: Pathogenic variant, confirmed in trans: 1","Number of Patients":1,"In trans Variants":["c.782G>A p.Arg261Gln"],"labels":"others"},{"CinGen ID":"CA251526","Variant Name":"NM_000277.2:c.331C>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26322415,"Raw Comment":"Detected in 13 patients with: c.611A>G, p.E280K, p.Y356*, p.V399V, p.Y154H, p.R158Q, p.R241C, p.R243Q, p.G307D, p.A322T, p.I324N, p.R413P. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.","Number of Patients":13,"In trans Variants":["c.611A>G p.(Tyr204Cys)","p.E280K c.(838G>A)","p.Y356* c.(1068C>G)","p.V399V c.(1197A>C)","p.Y154H c.(460T>C)","p.R158Q c.(473G>A)","p.R241C c.(721C>T)","p.R243Q c.(728G>A)","p.G307D c.(920G>A)","p.A322T c.(964G>A)","p.I324N c.(971T>A)","p.R413P c.(1238G>C)"],"labels":"others"},{"CinGen ID":"CA16020996","Variant Name":"NM_001354304.2:c.1316-2A>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"Variant was found in trans with p.R241C (Pathogenic 7 reports) (PMID: 26322415). All mutations identified in patients were confirmed by analyzing parental DNA via Sanger automated sequencing.","Number of Patients":"NA","In trans Variants":["p.R241C c.(721C>T)"],"labels":"others"},{"CinGen ID":"CA16020751","Variant Name":"NM_000277.1:c.224A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"Patient genotype: p.[D75V];[R413P] - VarID592, Pathogenic. All mutations identified in patients were confirmed by analyzing\nparental DNA.","Number of Patients":1,"In trans Variants":["R413P c.(1238G>C)"],"labels":"others"},{"CinGen ID":"CA16020832","Variant Name":"NM_000277.3:c.659A>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26322415,"Raw Comment":"PMID 26322415: listed p.[A156P];[H220P] in one patient with classic PKU (Phe levels >20mg\/dl). All patients fulfilled the diagnostic criteria of PKU, with a blood phenylalanine concentration >2mg\/dl. BH4 deficiency was excluded byanalysis of urinary pterins and dihydropteridine reductase activity in erythrocytes.","Number of Patients":1,"In trans Variants":["p.A156P c.(466G>C)"],"labels":"others"},{"CinGen ID":"CA16020772","Variant Name":"NM_000277.3:c.353-2A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"c.[353-2A>T ];[331C>T ], p.[(?)];[R111*]. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.","Number of Patients":"NA","In trans Variants":["c.331C>T p.R111*"],"labels":"others"},{"CinGen ID":"CA16020761","Variant Name":"NM_000277.3:c.292T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"c.[292T>G];[1222C>T ], p.[L98V ];[R408W ]. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.","Number of Patients":"NA","In trans Variants":["c.1222C>T p.R408W"],"labels":"others"},{"CinGen ID":"CA229875","Variant Name":"NM_000277.1:c.964G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26322415,"Raw Comment":"147 patients. A single patient with this variant c.964G>A (p.A322T) \/ c.331C>T (pR111X) (pathogenic) with mild hyperphenylalanemia (Phe <10mg\/dL)\nMethods \u00e2\u0080\u0093 All patients were picked up by NBS and BH4 defect was excluded in all patients with urine pterins and DHPR activity.","Number of Patients":1,"In trans Variants":["c.331C>T p.R111X"],"labels":"others"},{"CinGen ID":"CA16020799","Variant Name":"NM_001354304.1:c.478C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"Patient genotype: p.R241C;Q160*. All mutations identified in patients were confirmed by analyzing parental DNA.","Number of Patients":1,"In trans Variants":["p.R241C c.(721C>T)"],"labels":"others"},{"CinGen ID":"CA229653","Variant Name":"NM_000277.3:c.611A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26322415,"Raw Comment":"Detected in trans with R111* (2) c.442-1G>A R158W L255S P281L K363Nfs*37 V399V R408W R241C (2) R243Q R261Q (2) S349A R413P A434D (2) PMID: 26322415 >4 points","Number of Patients":"53","In trans Variants":["p.R111* c.(331C>T)","c.442-1G>A","p.R158W c.(472C>T)","p.L255S c.(764T>C)","p.P281L c.(842C>T)","p.K363Nfs ","p.V399V c.(1197A>C) c.(1197A>T) c.(1197A>G)","p.R408W c.(1222C>T)","p.R241C c.(721C>T)","p.R243Q c.(728G>A)","p.R261Q c.(782G>A)","p.S349A c.(1045T>G)","p.R413D"],"labels":"others"},{"CinGen ID":"CA16020971","Variant Name":"NM_001354304.2:c.1215_1219del","Condition":"phenylketonuria","Criterion":"PM3","PMID":26322415,"Raw Comment":"Variant was found in trans with p.P147L (Likely Pathogenic 3 reports) in a patient with mPKU. (PMID: 26322415). Parental DNA was sequenced via NGS.","Number of Patients":1,"In trans Variants":["p.P147L c.(440C>T)"],"labels":"others"},{"CinGen ID":"CA262105","Variant Name":"NM_206933.2:c.5581G>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":26338283,"Raw Comment":"67 Chinese families with Usher syndrome were tested for variants in 196 retinal disease genes. The p.Gly1861Ser variant was identified 1 patient with c.8559-2A>G in trans.","Number of Patients":1,"In trans Variants":["c.8559-2A>G"],"labels":"eval"},{"CinGen ID":"CA262122","Variant Name":"NM_206933.2:c.8559-2A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":26338283,"Raw Comment":"This study of 67 Chinese Usher syndrome probands identified 11 probands with the variant. They declare that the variant is a founder mutation that accounts for 265 of all Western Japanese USH patients but was never observed in Europeans. The varaint was observed in 5 individuals who were compound het via missense and 6 individuals with nonsense or frameshift variants.","Number of Patients":11,"In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA229481","Variant Name":"NM_000277.2:c.199T>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26351554,"Raw Comment":"A total of 218 alleles from109 individuals from 40 PKU families (40 PKU patients and their parents) were tested for S67P. Observed mutations in the patients were inherited from their parents. s67p\/s67p; 2 patients, s67p\/ivs10nt-11: 7 patients; s67p\/r261q: 3 patients; r408q\/s67p: 1 patient; s67p\/r252w: 1 patient.","Number of Patients":14,"In trans Variants":["S67P c.(199T>C)","S67P c.(199T>C)","IVS10nt-11","IVS10nt-11","IVS10nt-11","IVS10nt-11","IVS10nt-11","IVS10nt-11","IVS10nt-11","R261Q c.(782G>A)","R261Q c.(782G>A)","R261Q c.(782G>A)","R408Q c.(1223G>A)","R252W c.(754C>T)"],"labels":"eval"},{"CinGen ID":"CA481331323","Variant Name":"NM_001354304.2:c.843T>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26413448,"Raw Comment":"This variant was detected with pathogenic variant c.168+5G>C in a patient with PKU (PMID: 26413448). points=0.5.\n","Number of Patients":1,"In trans Variants":["c.168+5G>C"],"labels":"eval"},{"CinGen ID":"CA229845","Variant Name":"NM_000277.2:c.912G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26413448,"Raw Comment":"Detected on 2 alleles (table 2, \"polymorphism\", 2.56% frequency in cohort), once in a patient with genotype c.838G>Ap.E280K\/c.838G>Ap.E280K","Number of Patients":1,"In trans Variants":["c.838G>A p.E280K"],"labels":"eval"},{"CinGen ID":"CA229821","Variant Name":"NM_000277.2:c.848T>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26413448,"Raw Comment":"Single patient, homozygous, with classic PKU","Number of Patients":1,"In trans Variants":["homozygous c.848T>A p.(Ile283Asn) p.(Ile283Asn)"],"labels":"eval"},{"CinGen ID":"CA229453","Variant Name":"NM_000277.2:c.168+5G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26413448,"Raw Comment":"c.168+5G>A was observed in the homozygous state in one proband.","Number of Patients":1,"In trans Variants":["homozygous c.168+5G>A"],"labels":"eval"},{"CinGen ID":"CA229667","Variant Name":"NM_000277.2:c.632delC","Condition":"phenylketonuria","Criterion":"PM3","PMID":26413448,"Raw Comment":"single patient described with classic PKU","Number of Patients":1,"In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA16020836","Variant Name":"NM_000277.1:c.676C>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26481238,"Raw Comment":"PMID 26481238: Table 1 listed c.168+5G>C\/p.Gln226Lys in one patient with Phe 1212uM.","Number of Patients":1,"In trans Variants":["c.168+5G>C"],"labels":"fine-tune"},{"CinGen ID":"CA16020863","Variant Name":"NM_000277.1:c.803A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":26481238,"Raw Comment":"Y268C seen with Glu178Gly (VarID 92746, Pathogenic).","Number of Patients":1,"In trans Variants":["p.Glu178Gly c.(533A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA392260686","Variant Name":"NM_001321015.2:c.242G>A","Condition":"AGAT deficiency","Criterion":"PM3-Supporting","PMID":26490222,"Raw Comment":"Found as a homozygous variant in 3 affected siblings (PMID: 26490222) (0.5pts; PM3_Supporting) ","Number of Patients":3,"In trans Variants":["homozygous c.242G>A p.(Trp81*)"],"labels":"fine-tune"},{"CinGen ID":"CA392261143","Variant Name":"NM_001321015.2:c.166G>C","Condition":"AGAT deficiency","Criterion":"PM3-Supporting","PMID":26490222,"Raw Comment":"PMID: 26490222: Found in a single patient who was homozygous for the variant (0.5pts)","Number of Patients":1,"In trans Variants":["homozygous c.166G>C p.(Ala56Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA229617","Variant Name":"NM_000277.2:c.545A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":26542770,"Raw Comment":"PMID: 26542770. Two sibs with c.782G>A (p.R261Q) (pathogenic per ClinVar) Parental testing confirmed","Number of Patients":2,"In trans Variants":["c.782G>A p.R261Q"],"labels":"fine-tune"},{"CinGen ID":"CA16020973","Variant Name":"NM_001354304.2:c.1228T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":26542770,"Raw Comment":"PMID: 26542770 - F410I detected in trans in with c.1315+1G>A, reported as Pathogenic in ClinVar, confirmed in trans (VarID:576, 19 submitters) - 1.0 points.","Number of Patients":1,"In trans Variants":["c.1315+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA114368","Variant Name":"NM_000277.2:c.293T>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26542770,"Raw Comment":"Detected as homozygous, confirmed by parental testing PMID: 26542770","Number of Patients":1,"In trans Variants":["homozygous c.293T>C p.(Leu98Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA16020812","Variant Name":"NM_000277.3:c.532G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26542770,"Raw Comment":"detected in trans with F39del. Parental testing confirmed that the two mutations identified in the 368 patients all were present in trans.","Number of Patients":368,"In trans Variants":["p.F39del"],"labels":"fine-tune"},{"CinGen ID":"CA16020848","Variant Name":"NM_000277.1:c.730C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":26542770,"Raw Comment":"P244S in trans with R158Q (VarID 587, Pathogenic). Parental testing confirmed that the two mutations identified in the 368 patients all were present in trans.","Number of Patients":1,"In trans Variants":["p.R158Q c.(473G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229722","Variant Name":"NM_000277.2:c.733G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26542770,"Raw Comment":"V245M detected in trans with c.532G>A, p.E178G (VarID 92746, Pathogenic). Parental testing confirmed that the two mutations identified in the 368 patients all were present in trans.","Number of Patients":1,"In trans Variants":["c.532G>A p.E178G"],"labels":"fine-tune"},{"CinGen ID":"CA114362","Variant Name":"NM_000277.1:c.1241A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26542770,"Raw Comment":"compound het","Number of Patients":"NA","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA401325116","Variant Name":"NM_000152.5:c.2407C>T","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":26572913,"Raw Comment":"One patient is compound heterozygous for the variant and \"IVS 0-45T>G\" (assumed to be c.-32-13T>G), a pathogenic variant in GAA; phase unknown (PMID: 26572913). 0.5 points (PM3_Supporting).","Number of Patients":1,"In trans Variants":["IVS0-45T>G"],"labels":"fine-tune"},{"CinGen ID":"CA229598","Variant Name":"NM_000277.2:c.511G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26600521,"Raw Comment":"EX6-96G>A (c.611A>G) (P\/LP) maternal, G171R paternal","Number of Patients":1,"In trans Variants":["EX6-96G>A c.611A>G"],"labels":"fine-tune"},{"CinGen ID":"CA16020762","Variant Name":"NM_000277.2:c.301G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26600521,"Raw Comment":"Table 4. Family 86. Proband genotype: D101N\/Q267E (VarID102839, no clinical significance provided)","Number of Patients":1,"In trans Variants":["p.Q267E c.(799C>G)"],"labels":"fine-tune"},{"CinGen ID":"CA275338","Variant Name":"NM_000277.2:c.526C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26600521,"Raw Comment":"Identified in 6 patients, in trans with R243Q and R241C (both pathogenic)","Number of Patients":6,"In trans Variants":["p.R243Q c.(728G>A)","p.R241C c.(721C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229285","Variant Name":"NM_000277.2:c.1030G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":26600521,"Raw Comment":"Seen in an individual and fetus in trans with Q419R. Not found in Clinvar.","Number of Patients":1,"In trans Variants":["p.Q419R c.(1256A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229769","Variant Name":"NM_000277.2:c.799C>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":26600521,"Raw Comment":"Proband genotype: D101N (paternal)\/Q267E (Maternal).","Number of Patients":1,"In trans Variants":["p.D101N c.(301G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA267632","Variant Name":"NM_000277.1:c.1180G>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"Asp394Tyr seen with 1066-3C\u00e2\u0080\u0089>\u00e2\u0080\u0089T in 1 PKU patient and Thr380Met (VarID 628, Pathogenic\/Likely Pathogenic in ClinVar) in a 2nd patient.","Number of Patients":2,"In trans Variants":["c.1066-3C>T","p.Thr380Met c.(1139C>T)"],"labels":"eval"},{"CinGen ID":"CA286508","Variant Name":"NM_000277.2:c.812A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"Patient genotype: [His271Arg]; [Arg408Trp].","Number of Patients":1,"In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"eval"},{"CinGen ID":"CA267656","Variant Name":"NM_000277.2:c.504C>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"The proband was said to be heterozygous for the variant and also harbor the known pathogenic allele (per ClinGen PAH working group classification, see ClinVar ID 92751) c. 898G > T (p.Ala300Ser) variant; however, the manuscript did not specify whether the phase of the variants was confirmed via parental testing.","Number of Patients":1,"In trans Variants":["c.898G>T p.Ala300Ser"],"labels":"eval"},{"CinGen ID":"CA267639","Variant Name":"NM_000277.2:c.164T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"Patient genotype: c. [164T>C]; [1066-11G>A].","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"eval"},{"CinGen ID":"CA229667","Variant Name":"NM_000277.2:c.632delC","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"in trans","Number of Patients":"NA","In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA229669","Variant Name":"NM_000277.3:c.648C>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"At least one patient has been reported (PMID: 26666653) compound heterozygous for Tyr216Ter and Glu280Lys (ClinVar 580, Pathogenic by multiple submitters). Confirmation of trans phase was not reported.","Number of Patients":1,"In trans Variants":["p.Glu280Lys c.(838G>A)"],"labels":"eval"},{"CinGen ID":"CA229632","Variant Name":"NM_000277.3:c.578_579CT[1]","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"At least one patient has been reported (PMID: 26666653) compound heterozygous for c.580_581del and Leu348Val (ClinVar 92727, Pathogenic by multiple submitters). Confirmation of trans phase was not reported.","Number of Patients":1,"In trans Variants":["p.Leu348Val c.(1042C>G)"],"labels":"eval"},{"CinGen ID":"CA220584","Variant Name":"NM_000277.2:c.500A>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26666653,"Raw Comment":"Genotype: c. [500A > T] (p.Asn167Ile); [1066-11G > A].","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"eval"},{"CinGen ID":"CA267658","Variant Name":"NM_000277.2:c.547_548delGAinsTT","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"This variant has been observed in trans with the previously assessed pathogenic variant c.143T>C; p.Leu48Ser (ClinVar 608, Pathogenic).","Number of Patients":1,"In trans Variants":["c.143T>C p.Leu48Ser"],"labels":"eval"},{"CinGen ID":"CA251535","Variant Name":"NM_000277.3:c.281_283TCA[1]","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26666653,"Raw Comment":"This variant was documented in a French patient diagnosed with mild hyperphenylalaninemia (MHP, 180 < Phe < 600 \u00ce\u00bcmol\/L) who was a compound heterozygote with the pathogenic c.1243G>A variant in trans; this variant was also found in a patient diagnosed with classic PKU (cPKU, Phe > 1200 \u00ce\u00bcmol\/L) who was a compound heterozygote with the pathogenic c.441+5G>T variant in trans (PMID: 26666653). In this paper, the variant is referred to as \u00e2\u0080\u0098c.284_286delTCA\u00e2\u0080\u0099, which is the same as the \u00e2\u0080\u0098c.281_283delTCA\u00e2\u0080\u0099 variant. Parental analysis was not performed to confirm heterozygosity.","Number of Patients":2,"In trans Variants":["c.1243G>A p.(Asp415Asn)","c.441+5G>T"],"labels":"eval"},{"CinGen ID":"CA229315","Variant Name":"NM_000277.3:c.1065+1G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"The PAH variant c.1065+1G>A (IVS10+1G>A) was identified in two French patients with mild hyperphenylalaninemia (mHP, 180 < Phe < 600 \u00ce\u00bcmol\/L) with the PHA likely pathogenic variant c.261C>A (p.Ser87Arg)(ClinVar ID: 583) PM3 Points: 1*0.25=0.25 and with the PAH pathogenic variant c.1169A>G (p.Glu390Gly)(ClinVar ID: 625) PM3 Points: 1*0.5=0.5 (PM3 Points: 0.75_Supporting). Tetrahydrobiopterin (BH4) deficiency was excluded through a BH4 loading test (PMID: 26666653).","Number of Patients":2,"In trans Variants":["c.261C>A (p.Ser87Arg)","c.1169A>G (p.Glu390Gly)"],"labels":"eval"},{"CinGen ID":"CA220587","Variant Name":"NM_000277.1:c.841C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26666653,"Raw Comment":"Patient genotype: c. [841C>T]; [1315+1G>A] (VarID576, Pathogenic).","Number of Patients":1,"In trans Variants":["c.1315+1G>A"],"labels":"eval"},{"CinGen ID":"CA267669","Variant Name":"NM_000277.2:c.682G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"Seen in 1 patient with c.1066-11G>A (pathogenic in ClinVar)","Number of Patients":1,"In trans Variants":["c.1066-11G>A"],"labels":"eval"},{"CinGen ID":"CA267689","Variant Name":"NM_000277.2:c.931_932del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"The c.931_932del frameshift variant was observed in trans with the pathogenic variant Arg241Cys (ClinVar 102803, Pathogenic). Parental testing was not performed.","Number of Patients":1,"In trans Variants":["p.Arg241Cys c.(721C>T)"],"labels":"eval"},{"CinGen ID":"CA267677","Variant Name":"NM_000277.2:c.837del","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"The c.837del frameshift variant (in this publication misidentified as His280Asnfs*61) was observed in trans with the pathogenic variant c.1315+1G>A (ClinVar 576, Pathogenic).","Number of Patients":1,"In trans Variants":["c.1315+1G>A"],"labels":"eval"},{"CinGen ID":"CA229610","Variant Name":"NM_000277.3:c.529G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":26666653,"Raw Comment":"c. [529G>C]; [561G>A] p.[Val177Leu];[Trp187*]. parental testing not reported.","Number of Patients":0,"In trans Variants":["c.561G>A p.Trp187*"],"labels":"eval"},{"CinGen ID":"CA229539","Variant Name":"NM_000277.2:c.434A>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26666653,"Raw Comment":"Genotype: c. [434A>T]; [1222C>T]\/p. [Asp145Val];[Arg408Trp]","Number of Patients":1,"In trans Variants":["c.1222C>T p.Arg408Trp"],"labels":"eval"},{"CinGen ID":"CA229759","Variant Name":"NM_000277.1:c.782G>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":26666653,"Raw Comment":"Table1: p. [Ile65Thr] (Pathogenic in ClinVar;VarID 636); [Arg261Pro]. p. [Arg158Trp]; [Arg261Pro]. p. [Arg261Gln]; [Arg261Pro]. p. [Arg261Pro]; [Tyr414Cys]. c. [782G > C]; [1315 + 1G > A]. Parental analysis not reported.","Number of Patients":"NA","In trans Variants":["p.Ile65Thr c.(194T>C)","p.Arg158Trp c.(472C>T)","p.Arg261Gln c.(782G>A)","p.Tyr414Cys c.(1241A>G)","c.782G>C p.(Arg261Pro)","c.1315+1G>A"],"labels":"eval"},{"CinGen ID":"CA220592","Variant Name":"NM_000277.1:c.926C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"Genotype-phenotype association in French patients with PKU. 364 patients, 24hr BH4 loading test.","Number of Patients":364,"In trans Variants":["NA"],"labels":"eval"},{"CinGen ID":"CA267680","Variant Name":"NM_000277.3:c.869A>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"Found in one proband with classic PKU in presumed trans with the p.Glu280Lys variant (ClinVar Pathogenic; see ID 580) (0.5 points; PM3_Supporting) (PMID: 26666653)","Number of Patients":1,"In trans Variants":["p.Glu280Lys c.(838G>A)"],"labels":"eval"},{"CinGen ID":"CA267645","Variant Name":"NM_000277.2:c.196G>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"Detected with c.1315+1G>A; however, the manuscript did not specify whether the phase of the variants was confirmed via parental testing.","Number of Patients":"NA","In trans Variants":["c.196G>T p.(Glu66*)","c.1315+1G>A"],"labels":"eval"},{"CinGen ID":"CA229527","Variant Name":"NM_000277.2:c.386A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"Patient genotype: c.194T>C;c.386A>G \/ p.(Ile65Thr);p.(Asp129Gly). Parental segregation not reported\/performed.","Number of Patients":1,"In trans Variants":["c.194T>C (p.Ile65Thr)"],"labels":"eval"},{"CinGen ID":"CA267682","Variant Name":"NM_000277.2:c.887A>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":26666653,"Raw Comment":"detected with the pathogenic variant c.1222C > T (p.Arg408Trp). Although the paper said that parental samples were collected in the study, it did not explicitly state whether the phase of the variants was confirmed via parental testing.","Number of Patients":"NA","In trans Variants":["c.1222C>T p.Arg408Trp"],"labels":"eval"},{"CinGen ID":"CA267687","Variant Name":"NM_000277.2:c.913-8A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"The c.913-8A>G intronic variant has been observed in trans with the previously assessed pathogenic variant c.1315+1G>A (ClinVar 576, Pathogenic).","Number of Patients":"NA","In trans Variants":["c.1315+1G>A"],"labels":"eval"},{"CinGen ID":"CA267671","Variant Name":"NM_000277.2:c.785T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":26666653,"Raw Comment":"c. [117C > G]; [785 T > G]\/p. [Phe39Leu];[Val262Gly]. F39L, VarID 605, Pathogenic","Number of Patients":1,"In trans Variants":["c.117C>G p.Phe39Leu"],"labels":"eval"},{"CinGen ID":"CA658824775","Variant Name":"NM_000152.5:c.437del","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":26693141,"Raw Comment":"This variant has been detected in at least 2 individuals with Pompe disease. Of those individuals, 1 was compound heterozygous for the variant and a pathogenic or likely pathogenic variant (p.Trp746X, PMID: 26693141, 0.5 pt) (PM3_Supporting).","Number of Patients":2,"In trans Variants":["p.Trp746X","homozygous c.437del p.(Met146Argfs*7)"],"labels":"eval"},{"CinGen ID":"CA2580096763","Variant Name":"NM_000215.4:c.2680+89G>A","Condition":"T-B+ severe combined immunodeficiency due to JAK3 deficiency","Criterion":"PM3-Supporting","PMID":26769277,"Raw Comment":"The variant has been found in the homozygous state in an individual with T-B+NK- SCID (PMID:26769277, 0.5 points).","Number of Patients":1,"In trans Variants":["homozygous c.2680+89G>A "],"labels":"fine-tune"},{"CinGen ID":"CA274281","Variant Name":"NM_000152.3:c.1548G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":26873529,"Raw Comment":"Patient 11 is compound heterozygous for c.1548G>A (p.Trp516Ter) and c.2799+4A>G. The phase of the variants is unknown. Residual GAA activity in leukocytes is 0.41\u00ce\u00bcmol\/g\/h (normal range 3\u00e2\u0080\u009320).","Number of Patients":1,"In trans Variants":["c.2799+4A>G"],"labels":"fine-tune"},{"CinGen ID":"CA252231","Variant Name":"NM_206933.4:c.956G>A","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":26969326,"Raw Comment":"1 proband het. with VUS variant c.5329C>T (p.Arg1777Trp)","Number of Patients":1,"In trans Variants":["c.5329C>T p.Arg1777Trp"],"labels":"eval"},{"CinGen ID":"CA262054","Variant Name":"NM_206933.2:c.1036A>C","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":26969326,"Raw Comment":"detected in trans with c.2299del","Number of Patients":1,"In trans Variants":["c.2299del p.(Glu767Serfs*21)"],"labels":"eval"},{"CinGen ID":"CA132727","Variant Name":"NM_000441.1:c.349C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":26969326,"Raw Comment":"1119 patients with hearing loss tested. Found one compound heterozygote with this variant in trans with a splicing c.-4+1G>C variant with severe to profound hearing loss, but not noted if they tested temporal bone imaging. Shouldn't be used for PM3, as the splice variant is VUS.","Number of Patients":1,"In trans Variants":["c.-4+1G>C"],"labels":"eval"},{"CinGen ID":"CA400032338","Variant Name":"NM_000212.3:c.1697G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":27098940,"Raw Comment":"1 homozygous proband reported in PMID: 27098940 meets criteria for PM3_Supporting","Number of Patients":1,"In trans Variants":["homozygous c.1697G>A p.(Gly566Asp)"],"labels":"fine-tune"},{"CinGen ID":"CA386294434","Variant Name":"NM_000277.3:c.865G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"PM3_met: This variant was detected in trans with the pathogenic PAH variant p.Gly272* in 1 patient with classic PKU. This variant was detected in trans with the likely pathogenic PAH variant p.Arg155Cys in 1 patient with mild hyperphenylalaninemia (MHP)(Arg155Cys variant is also being curated by PAH EP). Parental analysis was performed for both variants to confirm compound heterozygosity. (PMID: 27121329)","Number of Patients":2,"In trans Variants":["p.Arg155Cys c.(463C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229453","Variant Name":"NM_000277.2:c.168+5G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":27121329,"Raw Comment":"Two probands were compound heterozygous for c.168+5G>A and either I65T (ClinVar 636, Pathogenic) or S349P (ClinVar 615, Pathogenic\/Likely Pathogenic).","Number of Patients":2,"In trans Variants":["p.S349P c.(1045T>C)","p.I65T c.(194T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229527","Variant Name":"NM_000277.2:c.386A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"2 patients reported: 1 homozygous; patient 2: c.1066-11G4A; p.Asp129Gly. Segregation analysis was done to rule out the presence of large genomic rearrangements.","Number of Patients":2,"In trans Variants":["homozygous c.386A>G p.(Asp129Gly)","p.Asp129Gly c.(386A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229521","Variant Name":"NM_000277.3:c.353-6T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"Detected in trans with pathogenic variant p. Tyr414Cys in a patient with mild PKU. Parental analysis was done (PMID 27121329).","Number of Patients":1,"In trans Variants":["p.Tyr414Cys,c.(1241A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA229532","Variant Name":"NM_000277.2:c.3G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":27121329,"Raw Comment":"Same patients as Bueno, et al. Patients\u00e2\u0080\u0099 and their families\u00e2\u0080\u0099 genomic DNA was obtained from whole-blood samples and\/or dried blood spots. Segregation analysis was done to rule out the presence of large genomic rearrangements.","Number of Patients":"NA","In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA229312","Variant Name":"NM_000277.3:c.1056del","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":27121329,"Raw Comment":"Detected in trans with 4 pathogenic variants (p. Ala403Val, p.Ile306Val, c.1066-11G>A; and p.Glu280Lys (PMID 27121329)).","Number of Patients":"4","In trans Variants":["p.Ala403Val c.(1208C>T)","p.Ile306Val c.(916A>G)","c.1066-11G>A","p.Glu280Lys c.(838G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA16020791","Variant Name":"NM_000277.3:c.443G>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"Detected in trans with p.Ser349Pro (pathogenic 5 submitters). Segregation analysis was done. PMID: 27121329","Number of Patients":1,"In trans Variants":["p.Ser349Pro c.(1045T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA229543","Variant Name":"NM_000277.2:c.440C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":27121329,"Raw Comment":"Patient genotype: p.[Arg261*];[Pro147Leu]. Segregation analysis was done to rule out the presence of large genomic rearrangements.","Number of Patients":1,"In trans Variants":["p.Arg261* c.(781C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229448","Variant Name":"NM_000277.3:c.161T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"Detected in trans with pathogenic variant c.912+1G>A (6 submitters) Segregation analysis was done. PMID: 27121329","Number of Patients":1,"In trans Variants":["c.912+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA229656","Variant Name":"NM_000277.1:c.613G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":27121329,"Raw Comment":"p.[Glu205Lys];[Arg243*] in one mild-moderate PKU (Phe 600-1200umol\/L) and one classic PKU patient (Phe >1200umol\/L).","Number of Patients":1,"In trans Variants":["p.Arg243* c.(727C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229836","Variant Name":"NM_000277.2:c.889C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"Detected in the homozygous state in 1 patient. Segregation analysis was done to rule out the presence of large genomic rearrangements.","Number of Patients":1,"In trans Variants":["homozygous c.889C>T p.(Arg297Cys)"],"labels":"fine-tune"},{"CinGen ID":"CA114371","Variant Name":"NM_000277.3:c.527G>T","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":27121329,"Raw Comment":"p.[Arg176Leu];[Phe39del] (n=2), p.[Arg176Leu];[Leu48Ser] (n=2), p.[Arg176Leu];[Tyr277Asp], p.[Arg243*];[Arg176Leu] (n=3), p.[Arg176Leu];[Arg243Gln], p.[Arg176Leu];[Tyr414Cys] (n=3), p.[Arg176Leu];[Glu390Gly], p.[Arg176Leu];[Arg408Trp], p.[Arg176Leu];[Glu280Lys], c.[912G4A];p.[Arg176Leu], p.[Arg176Leu];[Arg261Gln] (n=4). Segregation analysis was done. PMID: 27121329","Number of Patients":19,"In trans Variants":["p.Arg408Trp c.(1222C>T)","p.Arg243* c.(727C>T)","p.Tyr277Asp c.(829T>G)","p.Arg261Gln c.(782G>A)","p.Arg243Gln c.(728G>A)","p.Leu48Ser c.(143T>C)","p.Glu280Lys c.(838G>A)","p.Glu390Gly c.(1169A>G)","c.912G>A;","p.Tyr414Cys c.(1241A>G)","p.Phe39del"],"labels":"fine-tune"},{"CinGen ID":"CA6748704","Variant Name":"NM_001354304.2:c.1259G>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"PMID: 27121329 - R420M detected with A403V (Pathogenic in ClinVar, VarID:92731, 18 submitters), phase known (segregation analysis performed) - 1.0 points","Number of Patients":1,"In trans Variants":["p.A403V c.(1208C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020956","Variant Name":"NM_000277.1:c.1171_1172del","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"detected in trans with p.[Ser349Pro] (P\/LP). Segregation analysis was done to rule out the presence of large genomic rearrangements. PMID: 27121329","Number of Patients":1,"In trans Variants":["p.Ser349Pro c.(1045T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA6748917","Variant Name":"NM_000277.3:c.463C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"p.[Arg155Cys];[Gly289Arg]. Segregation analysis was done. PMID=27121329","Number of Patients":"NA","In trans Variants":["p.Gly289Arg c.(865G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA16020780","Variant Name":"NM_001354304.2:c.364C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"Detected in trans with pathogenic variant p. Asp415Asn. Segregation analysis was done (PMID 27121329).","Number of Patients":1,"In trans Variants":["p.Asp415Asn c.(1243G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA229420","Variant Name":"NM_000277.3:c.1262T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":27121329,"Raw Comment":"Seen in a patient with mild PKU in trans with R241H, pathogenic in ClinVar 102804","Number of Patients":1,"In trans Variants":["p.R241H c.(722G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA16020876","Variant Name":"NM_000277.1:c.847A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"In trans with c.1045T>C (p.Ser349Pro) (pathogenic in ClinVar)","Number of Patients":1,"In trans Variants":["c.1045T>C p.Ser349Pro"],"labels":"fine-tune"},{"CinGen ID":"CA16020747","Variant Name":"NM_001354304.2:c.209C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"Detected in trans with pathogenic variant p.Ala300Ser. Segregation analysis was done (PMID 27121329).","Number of Patients":1,"In trans Variants":["p.Ala300Ser c.(898G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA220587","Variant Name":"NM_000277.1:c.841C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":27121329,"Raw Comment":"Patient genotype: p.[Arg243*];[Pro281Ser]. (VarID588, Pathogenic)","Number of Patients":1,"In trans Variants":["p.Arg243* c.(727C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229280","Variant Name":"NM_000277.3:c.1027T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":27121329,"Raw Comment":"Seen in trans with S349P, pathogenic\/likely pathogenic in Clinvar (Var ID: 615)","Number of Patients":1,"In trans Variants":["p.S349P c.(1045T>C)"],"labels":"fine-tune"},{"CinGen ID":"CA624860683","Variant Name":"NM_000018.4:c.253dup","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Supporting","PMID":27209629,"Raw Comment":"PM3_supporting met. This variant has been detected in one individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This individual was compound heterozygous for the variant and a pathogenic or likely pathogenic variant (VCV000021025.27; c.848T>C, p.(Val283Ala); not confirmed in trans by parental testing. (PM3 points = 0.5, PMID: 27209629) (PM3_Supporting).","Number of Patients":1,"In trans Variants":["c.848T>C, p.(Val283Ala)"],"labels":"eval"},{"CinGen ID":"CA275277","Variant Name":"NM_206933.2:c.8682-9A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":27318125,"Raw Comment":"1 homozygote with variant for 0.25 points under PM3. The homozygote was displayed in the supplemental table S2.","Number of Patients":1,"In trans Variants":["homozygous c.8682-9A>G "],"labels":"fine-tune"},{"CinGen ID":"CA274311","Variant Name":"NM_000152.4:c.1128_1129delGGinsC","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":27408821,"Raw Comment":"c.1128_1129delGGinsC was found in compound heterozygosity with a pathogenic variant, -32-13T>G (a known pathogenic variant), in an individual with late onset Pompe disease. The phase is unknown. No GAA activity data is available, and therefore this data will not be included.","Number of Patients":1,"In trans Variants":["-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA229845","Variant Name":"NM_000277.2:c.912G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":27413125,"Raw Comment":"Detected with R241H in subject 6. Parental testing not reported.","Number of Patients":1,"In trans Variants":["p.R241H c.(722G>A)"],"labels":"eval"},{"CinGen ID":"CA180669","Variant Name":"NM_000260.4:c.2476G>A","Condition":"Usher syndrome","Criterion":"PM3","PMID":27460420,"Raw Comment":"427 individuals with Usher syndrome from various European medical centers were exome sequenced. The p.Ala826Thr was identified in the homozygous state in one individual. This individual was also heterozygous for p.Ser3590Cys in ADGRV1.","Number of Patients":"2","In trans Variants":["homozygous c.2476G>A p.(Ala826Thr)","p.Ser3590Cys"],"labels":"eval"},{"CinGen ID":"CA184505","Variant Name":"NM_000260.3:c.3503G>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":27460420,"Raw Comment":"Patient with USH type 1 compound het for MYO7A:c.3503G4A \n (p.Arg1168Gln)+deletion of exon 46, and was\nheterozygous for USH2A:c.2299delG (p.Glu767Serfs*21). According to entry in LOVD USHbases, deletion of exon 46 is c.6238-?_6354+?del (in frame exon deletion)","Number of Patients":1,"In trans Variants":["USH2A:c.2299delG (p.Glu767Serfs*21)"],"labels":"eval"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":27541434,"Raw Comment":"This study identified 2 cases who were compound heterozygous for this variant out of 9317 Southern Chinese newborns. These individuals were part of 34 other indiivudals who had causal variants identiied in the paper but (most) passed newborn screening. One indiviudal had the p.Val659Leu variant in trans, while the other individual had the c.912-2A>G variant. Both are pathogenic.These two indiviudals did NOT pass the newborn screening and were foudn to have severe\/moderate hearing loss based on the referral. Most of the individuals that passed were m.1555A>G","Number of Patients":2,"In trans Variants":["p.Val659Leu c.(1975G>C)","c.912-2A>G"],"labels":"fine-tune"},{"CinGen ID":"CA115848","Variant Name":"NM_000419.4:c.641T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":27607598,"Raw Comment":"Patient was a compound heterozygote for c.641T>C (p.Leu214Pro) and pathogenic variant c.1234G>A (p.Gly412Arg). The variants were confirmed to be in trans by parental testing. However, to avoid circularity the proband was counted only towards the classification Gly412Arg not Leu214Pro.","Number of Patients":1,"In trans Variants":["c.1234G>A p.Gly412Arg"],"labels":"fine-tune"},{"CinGen ID":"CA8603182","Variant Name":"NM_000419.4:c.1234G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Strong","PMID":27607598,"Raw Comment":"The genotype was reported for one of the six Glanzmann Thrombasthenia patients; this patient was a compound heterozygote for the Pathogenic variant c.641T>C (p.Leu214Pro) and c.1234G>A (p.Gly412Arg). The variants were confirmed to be in trans by parental testing. 1pt","Number of Patients":1,"In trans Variants":["c.641T>C p.Leu214Pro"],"labels":"fine-tune"},{"CinGen ID":"CA115848","Variant Name":"NM_000419.4:c.641T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":27696190,"Raw Comment":"The proband in this paper is a compound heterozygote with this c.2602-3C>G splice variant and c.641T>C (Leu214Pro). To avoid circularity the proband was counted only towards the classification c.2602-3C>G not Leu214Pro.","Number of Patients":1,"In trans Variants":["c.2602-3C>G"],"labels":"fine-tune"},{"CinGen ID":"CA234050","Variant Name":"NM_000152.4:c.1841C>A","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":27708273,"Raw Comment":"Patient 1117 is compound heterozygous for c.1841C>A (p.Thr614Lys) and the known pathogenic variant, c.-32-13T>G identified by exome sequencing. The patient had a clinical diagnosis of limb girdle muscular dystrophy.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA023422","Variant Name":"NM_000527.5:c.1133A>C","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":27784735,"Raw Comment":"PMID: 27784735 - variant identified in two children with homozygous FH: in one patient confirmed in trans with LDLR p.Ile792Thr and in the second patient confirmed in trans with a LP\/P LDLR exonic deletion; given this exonic deletion is LP\/P, PM3 applies.","Number of Patients":2,"In trans Variants":["p.Ile792Thr c.(2375T>C)","LDLR exonic deletion"],"labels":"fine-tune"},{"CinGen ID":"CA023406","Variant Name":"NM_000527.5:c.1027G>A","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":27784735,"Raw Comment":"Variant meets PM2 and is identified in an index case with homozygous FH phenotype (untreated LDL-C > 500mg\/dL, or LDL-C > 300 mmol\/dL on high-intensive lipid-lowering therapy and the presence of tendon xanthomas before 10 year of age), reported by Sanchez-Hernandez et al, 2016, Universitario Insular Materno Infantil de Gran Canaria, Spain, PMID 27784735. This variant met enough pathogenic criteria toward Pathogenic classification by these guidelines before PM3 code applied.","Number of Patients":1,"In trans Variants":["homozygous c.1027G>A p.(Gly343Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA273892","Variant Name":"NM_000152.3:c.1933G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":27927596,"Raw Comment":"Patient 2 is compound heterozygous for c.1933G>A (p.Asp645Leu) and c.795delG. The phase of the variants is unknown. The diagnosis was \"confirmed by significantly reduced GAA activities in fibroblasts or lymphocytes\" however, individual GAA activity is not available and therefore this data will not be included.","Number of Patients":1,"In trans Variants":["c.795delG"],"labels":"fine-tune"},{"CinGen ID":"CA023436","Variant Name":"NM_000527.5:c.1216C>A","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":28028493,"Raw Comment":"Variant meets PM2 and is identified in one compound heterozygote with a homozygous FH phenotype published in PMID 28028493 (Patient F3 compound with NM_000527.5(LDLR):c.760C>T (p.Gln254Ter) (ClinVar ID 251436), LDLc: 18.21 mmol\/l). Additional variant classified as Pathogenic by these guidelines","Number of Patients":1,"In trans Variants":["c.760C>T p.Gln254Ter"],"labels":"eval"},{"CinGen ID":"CA10585116","Variant Name":"NM_000527.5:c.760C>T","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":28028493,"Raw Comment":"variant meets PM2 and was identified in 1 index case (Patient F3) with LDLc 18.21 mmol\/l and compound heterozygote with NM_000527.5(LDLR):c.1216C>A (p.Arg406=) from Du et al. 2016 (PMID: 28028493).\n-- 2nd variant is classified as Likely Pathogenic by these guidelines and patient has phenotype of homozygous FH, so PM3 is met","Number of Patients":1,"In trans Variants":["c.1216C>A p.Arg406="],"labels":"eval"},{"CinGen ID":"CA915940266","Variant Name":"NM_000419.5:c.175del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":28078347,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. One proband was homozygous for the variant (PMID:28078347). Total points: 0.5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.175del p.(Asp59Thrfs*52)"],"labels":"fine-tune"},{"CinGen ID":"CA891834518","Variant Name":"NM_001079804.3:c.2799+5G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":28265479,"Raw Comment":"One patient, with consanguineous parents, is reported to be homozygous for the variant (PMID: 28265479), 0.5 points, PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2799+5G>A"],"labels":"eval"},{"CinGen ID":"CA252010","Variant Name":"NM_000022.4:c.219-2A>G","Condition":"adenosine deaminase deficiency","Criterion":"PM3-Supporting","PMID":28266921,"Raw Comment":"The variant has been detected in 1 individual with SCID. The individual was homozygous for this variant. (0.5pt, PM3_Supporting, PMID 28266921)","Number of Patients":1,"In trans Variants":["homozygous c.219-2A>G "],"labels":"fine-tune"},{"CinGen ID":"CA402994004","Variant Name":"NM_138924.3:c.564G>T","Condition":"guanidinoacetate methyltransferase deficiency","Criterion":"PM3","PMID":28438604,"Raw Comment":"Patient comp het for GAMT c.491dupG (maternal) (path by CCDS VCEP w\/o using this occurrence; ClinVar ID: 495685) \/c.564G>T (pat) (PMID: 28438604)","Number of Patients":1,"In trans Variants":["c.491dupG p.(Val165Argfs*26)","c.564G>T p.(Met188Ile)"],"labels":"fine-tune"},{"CinGen ID":"CA261403","Variant Name":"NM_000441.1:c.1229C>T","Condition":"Pendred syndrome","Criterion":"PM3-Very Strong","PMID":28444304,"Raw Comment":"This study identified a compound heterozygous case with thyroid dysgenesis and p.T310M\/p.V678V variants in SLC26A4. The p.V678V variant occurs in the last bp of the last codon in exon 17\/21. This varaint is a VUS (already maxed to PM3_VS).","Number of Patients":1,"In trans Variants":["p.V678V"],"labels":"fine-tune"},{"CinGen ID":"CA404081052","Variant Name":"NM_000527.5:c.920A>G","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":28502510,"Raw Comment":"Variant meets PM2 and is identified in an index case with homozygous FH phenotype and homozygous for the NM_000527.5(LDLR):c.920A>G (p.Asp307Gly) variant (PMID: 28502510). \n","Number of Patients":1,"In trans Variants":["homozygous c.920A>G p.(Asp307Gly)"],"labels":"fine-tune"},{"CinGen ID":"CA658798978","Variant Name":"NM_000152.5:c.1153del","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":28554557,"Raw Comment":"One patient has been reported who meets the ClinGen LSD VCEP\u00e2\u0080\u0099s specifications for PP4 and who is compound heterozygous for the variant and c.-32-13T>G, phase unknown (28554557). PM3_Supporting is met (0.5 points)","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA16020983","Variant Name":"NM_000277.1:c.1250A>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":28593914,"Raw Comment":"detected with IVS10-11G>A. parental analysis not reported PMID: 28593914","Number of Patients":1,"In trans Variants":["IVS10-11G>A"],"labels":"fine-tune"},{"CinGen ID":"CA400029664","Variant Name":"NM_000212.3:c.1525C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":28748566,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann Thrombasthenia. For 1 of those individuals, 1 was compound heterozygous for this variant and a pathogenic variant not specified in trans (NM_000212.3(ITGB3):c.567del (p.Tyr190ThrfsTer17), PMID:28748566, CAID:CA8622982). Total points: .5 (PM3_Supporting). ","Number of Patients":1,"In trans Variants":["c.567del  p.Tyr190ThrfsTer17"],"labels":"eval"},{"CinGen ID":"CA291225782","Variant Name":"NM_000212.3:c.1639T>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":28748566,"Raw Comment":"Patient 3 reported in PMID: 28748566 is compound heterozygous for this variant and the ITGB3 variant c.1192delG (p.Ala398ProfsTer24, provisionally classified as pathogenic by the Platelet Disorders VCEP, trans phase not confirmed) (0.5 points, PM3_Supporting).","Number of Patients":1,"In trans Variants":["c.1192delG p.(Ala398Profs*24)"],"labels":"eval"},{"CinGen ID":"CA291240306","Variant Name":"NM_000212.2:c.31T>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":28748566,"Raw Comment":"Patient 1 is homozygous for the Trp11Arg variant.","Number of Patients":1,"In trans Variants":["homozygous c.31T>C p.(Trp11Arg)"],"labels":"eval"},{"CinGen ID":"CA229398","Variant Name":"NM_000277.2:c.1217T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":28754886,"Raw Comment":"Patient M1770: p.[IVS4-1G > A] (VarID 102671, P\/LP); [Ile406Thr].","Number of Patients":1,"In trans Variants":["p.IVS4-1G>A"],"labels":"eval"},{"CinGen ID":"CA229703","Variant Name":"NM_000277.3:c.707-1G>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":28754886,"Raw Comment":"The PAH variant c.707-1G>A (IVS6-1G>A) was detected in two Chinese patients with classic PKU (cPKU Phe more than 1200 \u00ce\u00bcmol\/L). These two patients were identified with another pathogenic variant in the PAH gene:\nc.1285C>A (p.Gln429Lys) (ClinVar ID: 551555) Likely Pathogenic (1*0.25=0.25)\nc.526C>T (p.Arg176Ter) (ClinVar ID: 102723) Pathogenic (PMID: 28754886) (1*0.5=0.5)","Number of Patients":2,"In trans Variants":["c.1285C>A (p.Gln429Lys)","c.526C>T (p.Arg176Ter)"],"labels":"eval"},{"CinGen ID":"CA1139532590","Variant Name":"NM_001354304.2:c.543_545del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":28754886,"Raw Comment":"c.[611A>G];[541-543delGAG]. Phase is unknown. PMID:28754886","Number of Patients":"NA","In trans Variants":["c.611A>G p.(Tyr204Cys)"],"labels":"eval"},{"CinGen ID":"CA16020794","Variant Name":"NM_000277.3:c.461A>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":28754886,"Raw Comment":"detected with pathogenic variant c.728G>A (p.Arg243Gln). The patient was compound heterozygous for the variant. parental analysis not reported. PMID: 28754886","Number of Patients":1,"In trans Variants":["c.728G>A (p.Arg243Gln)"],"labels":"eval"},{"CinGen ID":"CA16020742","Variant Name":"NM_000277.3:c.190_194del","Condition":"phenylketonuria","Criterion":"PM3","PMID":28754886,"Raw Comment":"The c.190_194delCACAT variant in PAH has been previously reported as a single variant, found in trans with the Likely Pathogenic (per internal PAH ClinGen Working Group classification -see PAH0095) p.Ala156Pro variant in a female Chinese proband with classic PKU (PM3) (PMID: 28754886)","Number of Patients":1,"In trans Variants":["p.Ala156Pro c.(466G>C)"],"labels":"eval"},{"CinGen ID":"CA287439291","Variant Name":"NM_000018.4:c.1220G>C","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3","PMID":28755359,"Raw Comment":"This variant has been reported as occurring in trans to a known pathogenic variant in a pair of siblings with positive newborn screens and reduced VLCAD activity (PMID: 28755359, PM3, PP4_moderate).","Number of Patients":2,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA10581303","Variant Name":"NM_000448.3:c.775del","Condition":"recombinase activating gene 1 deficiency","Criterion":"PM3-Supporting","PMID":28769923,"Raw Comment":"P28 of PMID: 28769923 is homozygous for this variant (0.5pt; PM3_supporting).\t","Number of Patients":1,"In trans Variants":["homozygous c.775del p.(Ser259Alafs*5)"],"labels":"eval"},{"CinGen ID":"CA16020812","Variant Name":"NM_000277.3:c.532G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":28771436,"Raw Comment":"Sample NBS47: c.1222C>T (R408W,P)\/c.532G>A. Parental testing not performed.","Number of Patients":1,"In trans Variants":["c.1222C>T p.R408W"],"labels":"fine-tune"},{"CinGen ID":"CA267693","Variant Name":"NM_000277.2:c.505C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":28771436,"Raw Comment":"Patient NBS51 was identified as compound heterozygous for c.505C>T and c.208_210del (ClinVar 102632, Pathogenic).","Number of Patients":1,"In trans Variants":["c.208_210del p.(Ser70del)"],"labels":"fine-tune"},{"CinGen ID":"CA399805578","Variant Name":"NM_000419.5:c.617T>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":28888044,"Raw Comment":"This variant was confirmed in the homozygous state in the patient. Parents were genotyped and were both heterozygous for this same variant (Patient 2 PMID: 28888044).","Number of Patients":1,"In trans Variants":["homozygous c.617T>A p.(Val206Asp)"],"labels":"fine-tune"},{"CinGen ID":"CA399796586","Variant Name":"NM_000419.4:c.2344C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":28888044,"Raw Comment":"Arg782Ter is curated as a variant identified in trans (phase not confirmed) with pathogenic variant Leu973Alafs in case No. 3.","Number of Patients":1,"In trans Variants":["p.Leu973Alafs"],"labels":"fine-tune"},{"CinGen ID":"CA8602531","Variant Name":"NM_000419.4:c.2915dup","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":28888044,"Raw Comment":"This variant was determined to be in trans with p.Arg584Ter in case No.1 and with Arg782Ter in case No. 3. Arg584Ter has been curated as a VUS, and does not meet PM2. Arg782Ter is curated as a pathogenic variant, the phase was not confirmed in Case 3. 0.5pt","Number of Patients":2,"In trans Variants":["p.Arg584Ter c.(1750C>T)","p.Arg782Ter c.(2344C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020966","Variant Name":"NM_000277.3:c.1200-1G>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":28915855,"Raw Comment":"This variant was documented with the pathogenic variant c.611A>G in one Thai patient diagnosed with Classic PKU (PMID: 28915855). The patient's neonatal phenylalanine screening level was 42.6 mg\/dL. The publication did not indicate whether parental analysis was performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["c.611A>G p.(Tyr204Cys)"],"labels":"eval"},{"CinGen ID":"CA184505","Variant Name":"NM_000260.3:c.3503G>A","Condition":"Usher syndrome","Criterion":"PM3-Strong","PMID":28944237,"Raw Comment":"Two patients with atypical usher syndrome. Patient 13: Arg1168Gln \/ 6025delG. Patient 14: Arg1168Gln \/ Leu1839Pro (vus).","Number of Patients":2,"In trans Variants":["c.6025delG p.(Ala2009Profs*32)","p.Leu1839Pro c.(5516T>C)"],"labels":"eval"},{"CinGen ID":"CA275277","Variant Name":"NM_206933.2:c.8682-9A>G","Condition":"Usher syndrome","Criterion":"PM3-Very Strong","PMID":28944237,"Raw Comment":"1 cpd het with Glu767SerfsX21 that is P by ClinVar (multiple submitters, no conflicts2 stars out of maximum of 4 stars). also identified 1 cpd het with Trp4175X also not classified not scored, and 1 additional het identified from same cohort (Germans)","Number of Patients":3,"In trans Variants":["p.Glu767SerfsX21","p.Trp4175X"],"labels":"eval"},{"CinGen ID":"CA386492906","Variant Name":"NM_001354304.2:c.1316-1G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the pathogenic variant p.Arg243Gln in a patient with cPKU (PMID:28982351). points=1.","Number of Patients":1,"In trans Variants":["p.Arg243Gln c.(728G>A)"],"labels":"others"},{"CinGen ID":"CA386296833","Variant Name":"NM_001354304.2:c.563G>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"Detected in trans with p.Val399= (P) 1.0pts PMID: 28982351","Number of Patients":1,"In trans Variants":["p.Val399="],"labels":"others"},{"CinGen ID":"CA386295265","Variant Name":"NM_001354304.2:c.804C>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"[p.Arg243Gln,p.Tyr268*]. Segregation analysis was done. PMID: 28982351","Number of Patients":"NA","In trans Variants":["p.Arg243Gln c.(728G>A)"],"labels":"others"},{"CinGen ID":"CA386296582","Variant Name":"NM_001354304.2:c.679C>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the pathogenic PAH variant p.Arg243Gln (1.0pt) PMID: 28982351","Number of Patients":1,"In trans Variants":["p.Arg243Gln c.(728G>A)"],"labels":"others"},{"CinGen ID":"CA386299735","Variant Name":"NM_001354304.2:c.442-2A>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the pathogenic variant c.441+3G>C in a patient with PKU (PMID:28982351). points=1.","Number of Patients":1,"In trans Variants":["c.441+3G>C"],"labels":"others"},{"CinGen ID":"CA386493446","Variant Name":"NM_001354304.2:c.1016C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the pathogenic variant p. Ex6-96A>G (evaluated by an expert panel and seen in multiple entries in ClinVar) in a patient with mPKU (PMID: 28982351). points=1.","Number of Patients":1,"In trans Variants":["p.Ex6-96A>G"],"labels":"others"},{"CinGen ID":"CA386493311","Variant Name":"NM_001354304.2:c.1096C>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the ClinVar likely pathogenic variant p.Gly247Arg in a patient with PKU (PMID: 28982351). points=1.","Number of Patients":1,"In trans Variants":["p.Gly247Arg c.(739G>C)"],"labels":"others"},{"CinGen ID":"CA386294521","Variant Name":"NM_001354304.2:c.843-1G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":28982351,"Raw Comment":"Detected in trans in 2 patients with pathogenic PAH variants p.S70del (P) 1.0pts and p.Arg243Gln (P) 1.0pts PMID: 28982351","Number of Patients":2,"In trans Variants":["p.S70del","p.Arg243Gln c.(728G>A)"],"labels":"others"},{"CinGen ID":"CA386296575","Variant Name":"NM_001354304.2:c.684A>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the pathogenic PAH variant p.Arg243Gln (1.0pt) PMID: 28982351","Number of Patients":1,"In trans Variants":["p.Arg243Gln c.(728G>A)"],"labels":"others"},{"CinGen ID":"CA386297078","Variant Name":"NM_001354304.2:c.510-1G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the pathogenic variant p.Arg111* in a patient with mPKU (PMID:28982351). points=1.","Number of Patients":1,"In trans Variants":["p.Arg111* c.(331C>T)"],"labels":"others"},{"CinGen ID":"CA386299729","Variant Name":"NM_001354304.2:c.442-1G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"Detected in trans with p.Val388Met (P) 1.0pts (PMID: 28982351)","Number of Patients":1,"In trans Variants":["p.Val388Met c.(1162G>A)"],"labels":"others"},{"CinGen ID":"CA1139532534","Variant Name":"NM_001354304.2:c.1200-3T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with pathogenic variant p.EX6-96A<G. Segregation analysis was done. PMID: 28982351","Number of Patients":1,"In trans Variants":["p.EX6-96A<G"],"labels":"others"},{"CinGen ID":"CA354151","Variant Name":"NM_000277.3:c.320A>G","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":28982351,"Raw Comment":"This variant was detected in trans with 16 pathogenic variants in patients with PKU; p.Arg111* (P) 1.0pts, p.Arg400Thr (P) 1.0pts, p.Val399= (P) 1.0pts, p.Val399= (P) 1.0pts, p.Arg241Cys (P) 1.0pts, p.Arg241Cys (P) 1.0pts, p.Arg413Pro (P) 1.0pts, p.Gly257Val (P) 1.0pts,, p.His107Arg 0.5 pts, p.Arg243Gln (P) 1.0pts, p.His220Pro (P) 1.0pts, p.Arg176* (P) 1.0pts,, p.Arg243Gln (P) 1.0pts, p.Arg243Gln (P) 1.0pts, p.Val230Ile (P) 1.0pts, p.Ile65Thr (P) 1.0pts PMID: 28982351","Number of Patients":16,"In trans Variants":["p.Arg111* c.(331C>T)","p.Arg400Thr c.(1199G>C)","p.Val399=","p.Val399=","p.Arg241Cys c.(721C>T)","p.Arg241Cys c.(721C>T)","p.Arg413Pro c.(1238G>C)","p.Gly257Val c.(770G>T)","p.His107Arg c.(320A>G)","p.Arg243Gln c.(728G>A)","p.His220Pro c.(659A>C)","p.Arg176* c.(526C>T)","p.Arg243Gln c.(728G>A)","p.Arg243Gln c.(728G>A)","p.Val230Ile c.(688G>A)","p.Ile65Thr c.(194T>C)"],"labels":"others"},{"CinGen ID":"CA229418","Variant Name":"NM_000277.3:c.1252A>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":28982351,"Raw Comment":"p.Arg243Gln (P 11 submitters), p.Arg408Gln (P 7 submitters), p.Arg176* (P 9 submitters), EX6-96A\u00ef\u00bc\u009eG (P 6 submitters), p.Tyr356*(P), p.Arg111* (P 6 submitters); variable sites in patient genes were aligned with the corresponding sites from the respective parents. PMID: 28982351","Number of Patients":5,"In trans Variants":["p.Arg243Gln c.(728G>A)","p.Arg408Gln c.(1223G>A)","EX6-96A\u00ef\u00bc\u009eG","p.Tyr356* c.(1068C>G)","p.Arg111* c.(331C>T)"],"labels":"others"},{"CinGen ID":"CA229445","Variant Name":"NM_000277.3:c.157C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"detected in trans with p.Arg158Gln (P) 1.0 pts PMID: 28982351","Number of Patients":1,"In trans Variants":["p.Arg158Gln c.(473G>A)"],"labels":"others"},{"CinGen ID":"CA229431","Variant Name":"NM_000277.3:c.1315+6T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":28982351,"Raw Comment":"This variant was documented in a mild PKU patient with the pathogenic p.Arg241His variant in trans. This variant was also documented in a patient with mild PKU with the likely pathogenic p.His107Arg variant in trans. This variant was documented in a mild PKU patient with the likely pathogenic c.722delG variant in trans. This variant was documented in a patient with mild PKU with the pathogenic p.Tyr356* variant in trans. Parental analysis was performed to confirm compound heterozygosity (PMID: 28982351).","Number of Patients":4,"In trans Variants":["p.Arg241His c.(722G>A)","p.His107Arg c.(320A>G)","c.722delG p.(Arg241Profs*100)","p.Tyr356* c.(1068C>G)"],"labels":"others"},{"CinGen ID":"CA229493","Variant Name":"NM_000277.3:c.231T>G","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"It has also been noted (PMID: 28982351) in a patient with mild PKU (plasma Phe 720 uM) and BH4 deficiency excluded (PP4_Moderate), who harbored it in trans with the p.Asp101Asn (Likely Pathogenic in ClinVar, ID 553851) and p.Gly247Arg (Likely Pathogenic in ClinVar, ID 102816) alleles (PM3). ","Number of Patients":1,"In trans Variants":["p.Asp101Asn c.(301G>A)","p.Gly247Arg c.(739G>C)"],"labels":"others"},{"CinGen ID":"CA16020733","Variant Name":"NM_001354304.1:c.168+2T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"Variant detected in one patient with a pathogenic missense (p.R243Q) in trans.","Number of Patients":1,"In trans Variants":["p.R243Q c.(728G>A)"],"labels":"others"},{"CinGen ID":"CA6748701","Variant Name":"NM_000277.1:c.1285C>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"Patient 328 has genotype EX6-96A>G (VarID 590; P\/LP)\/p.Gln429Lys. Peripheral blood samples were collected from the patients and parents in each of the 643 core families.","Number of Patients":1,"In trans Variants":["EX6-96A>G"],"labels":"others"},{"CinGen ID":"CA16020725","Variant Name":"NM_000277.3:c.61-3T>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the pathogenic PAH variant Arg111Ter in 1 patient with classic PKU (Phe > 1200 \u00c2\u00b5mol\/L). Parental analysis was performed to confirm compound heterozygosity (PMID: 28982351).","Number of Patients":1,"In trans Variants":["p.Arg111Ter c.(331C>T)"],"labels":"others"},{"CinGen ID":"CA229543","Variant Name":"NM_000277.2:c.440C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":28982351,"Raw Comment":"3 patients with p.Pro147Leu in trans with: S70del; p.His170Arg; p.Arg53His. Peripheral blood samples were collected from the patients and parents. Variable sites in patient genes were aligned with the corresponding sites from the respective parents.","Number of Patients":3,"In trans Variants":["p.S70del","p.His170Arg c.(509A>G)","p.Arg53His c.(158G>A)"],"labels":"others"},{"CinGen ID":"CA386493436","Variant Name":"NM_001354304.2:c.1023G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the pathogenic variant p.Ala434Asp (PMID: 28982351). points=1.","Number of Patients":1,"In trans Variants":["p.Ala434Asp c.(1301C>A)"],"labels":"others"},{"CinGen ID":"CA229430","Variant Name":"NM_000277.3:c.1315+4A>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":28982351,"Raw Comment":"This variant was documented in 1 PKU patient with the pathogenic c.1197A>T (p.V399V) variant in trans. This study included 655 PKU patients and phenylalanine plasma concentrations >120 \u00c2\u00b5mol\/L were reported for all subjects. Tetrahydrobiopterin (BH4) deficiency was excluded through urinary pterin analysis. Parental analysis was performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["c.1197A>T (p.V399V)"],"labels":"others"},{"CinGen ID":"CA6748745","Variant Name":"NM_001354304.2:c.1084C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant was detected in trans with the ClinVar reported pathogenic variant p.Arg413Pro in a patient with cPKU (PMID: 28982351). points=1.","Number of Patients":1,"In trans Variants":["p.Arg413Pro c.(1238G>C)"],"labels":"others"},{"CinGen ID":"CA229546","Variant Name":"NM_000277.3:c.441+3G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":28982351,"Raw Comment":"This variant was documented in one patient with classic PKU, with the likely pathogenic p.Ala434Asp variant in trans. This variant was documented in one patient with mild PKU, with the VUS Leu444Phe in trans. This variant was documented in one patient with PAH deficiency, with the IVS4-2A>G variant in trans. This variant was documented in one patient with mild hyperphenylalaninemia (MHP), the variant in trans was not specified. This variant was documented in one patient with mild PKU, with the pathogenic p.Arg400Thr variant in trans. Parental analysis was performed to confirm compound heterozygosity.","Number of Patients":5,"In trans Variants":["p.Ala434Asp c.(1301C>A)","p.Leu444Phe c.(1330C>T)","p.IVS4-2A>G","p.Arg400Thr c.(1199G>C)"],"labels":"others"},{"CinGen ID":"CA229622","Variant Name":"NM_000277.2:c.559T>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":28982351,"Raw Comment":"found in trans with p.Gln419Arg (classified LP by Counsyl in ClinVar) allele in 1 case with mild hyperphenylalanemia","Number of Patients":1,"In trans Variants":["p.Gln419Arg c.(1256A>G)"],"labels":"others"},{"CinGen ID":"CA1139532533","Variant Name":"NM_001354304.2:c.912+16T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":28982351,"Raw Comment":"This variant is detected in trans with pathogenic variant p.Arg111*. Segregation analysis was done. PMID: 28982351","Number of Patients":1,"In trans Variants":["p.Arg111* c.(331C>T)"],"labels":"others"},{"CinGen ID":"CA399799766","Variant Name":"NM_000419.5:c.2063C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":28983057,"Raw Comment":"This variant was observed in homozygosity in one individual (Case 36 in PMID: 28983057), earning 0.5 points and sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2063C>T p.(Ala688Val)"],"labels":"eval"},{"CinGen ID":"CA913189248","Variant Name":"NM_000419.4:c.2965del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":28983057,"Raw Comment":"Case 37 is a compound heterozygote for the pathogenic variant Val982Met and c.2965del frameshift variant. No confirmation was reported that the variants are in trans phase. 0.5pt","Number of Patients":1,"In trans Variants":["p.Val982Met c.(2944G>A)"],"labels":"eval"},{"CinGen ID":"CA16608466","Variant Name":"NM_000419.4:c.2944G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":28983057,"Raw Comment":"Case 37 is a compound heterozygote for this Val982Met variant and a c.2965del frameshift variant. No confirmation was reported that the variants are in trans phase. However, to avoid circularity the proband was counted only towards the classification of c.2965del not Val982Met.","Number of Patients":1,"In trans Variants":["c.2965del p.(Ala989Profs*?)"],"labels":"eval"},{"CinGen ID":"CA915940608","Variant Name":"NM_000212.3:c.1986dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29084015,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. One proband was homozygous for the variant (PMID:29084015). Total points: .5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1986dup p.(Asp663*)"],"labels":"fine-tune"},{"CinGen ID":"CA915940264","Variant Name":"NM_000419.5:c.113del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29084015,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann Thrombasthenia. One proband was homozygous for the variant (PMID:29084015). Total points: .5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.113del p.(Gln38Argfs*73)"],"labels":"fine-tune"},{"CinGen ID":"CA915940263","Variant Name":"NM_000212.3:c.1185del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29084015,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. 1 proband was homozygous for the variant (PMID:29084015). Total points: .5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1185del p.(Phe396Serfs*26)"],"labels":"fine-tune"},{"CinGen ID":"CA10605404","Variant Name":"NM_000152.3:c.2501_2502delCA","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":29122469,"Raw Comment":"One patient with infantile onset Pompde Disease is a compound heterozygote for c.2501_2502delCA and c.546+2_5delTGGG in GAA. However, the phase of the variants was not confirmed and the patient does not meet PP4 (0 points).","Number of Patients":1,"In trans Variants":["c.546+2_5delTGGG"],"labels":"eval"},{"CinGen ID":"CA274281","Variant Name":"NM_000152.3:c.1548G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":29122469,"Raw Comment":"Two patients with late-onset Pompe disease are reported who are compound heterozygous for c.1548G>A (p.Trp516Ter) and the known pathogenic variant c.-32-13T>G. The phase of the variants is unknown. Patients have a confirmed enzymatic diagnosis of Pompe disease meeting PP4 (personal communication); however, this data will not be included for PM3 because another patient with the same genotype, phase not confirmed, has already been included.","Number of Patients":2,"In trans Variants":["c.-32-13T>G","c.-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA273892","Variant Name":"NM_000152.3:c.1933G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":29122469,"Raw Comment":"Two individuals homozygous for c.1933G>A (p.Asp645Asn) and one compound heterozygous for this variant and c.2815_2816delGT(p.Val939fs*78) are reported. The phase of the variants is unknown. All have been enzymatically confirmed with Pompe disease.","Number of Patients":"err","In trans Variants":["homozygous c.1933G>A p.(Asp645Asn)","c.2815_2816delGT p.Val939fs*78"],"labels":"eval"},{"CinGen ID":"CA229343","Variant Name":"NM_000277.3:c.1099del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":29176022,"Raw Comment":"Patient 33 of PMID: 29176022 is compound heterozygous for the c.1099del variant and Arg241Cys (ClinVar 102803, Pathogenic with expert panel review). Confirmation of trans phase was not reported. 0.5pt","Number of Patients":1,"In trans Variants":["p.Arg241Cys c.(721C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA891862619","Variant Name":"NM_001079804.3:c.1057del","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":29181627,"Raw Comment":"This variant has been detected in an individual with Pompe disease who is compound heterozygous for the variant and a variant classified as pathogenic by the ClinGen LSD VCEP, c.784G>A (p.Glu262Lys), phase unconfirmed (PMID 29181627)(0.5 points; PM3_Supporting).","Number of Patients":1,"In trans Variants":["c.784G>A (p.Glu262Lys)"],"labels":"eval"},{"CinGen ID":"CA16608675","Variant Name":"NM_000152.4:c.1478C>T","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":29181627,"Raw Comment":"Patient 21 is a compound heterozygote for c.1478C>T and c.1134C>G in GAA. The phase of the variants was not confirmed. GAA activity in the patient was not specified (0 points).","Number of Patients":1,"In trans Variants":["c.1134C>G p.(Tyr378*)"],"labels":"eval"},{"CinGen ID":"CA274281","Variant Name":"NM_000152.3:c.1548G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":29181627,"Raw Comment":"Patient 16 is compound heterozygous for c.1548G>A (p.Trp516Ter) and c.1470G>A (p.Phe490Leu). The phase of the variants is unknown. Residual GAA activity was not provided and therefore this data will not be included for PM3. The patient is on enzyme replacement therapy.","Number of Patients":1,"In trans Variants":["c.1470G>A (p.Phe490Leu)"],"labels":"eval"},{"CinGen ID":"CA253314","Variant Name":"NM_000441.1:c.-103T>C","Condition":"Pendred syndrome","Criterion":"PM3","PMID":29196752,"Raw Comment":"Patient S1536 in supplemental table 2 is a 5 year old proband with congenital, sporadic, moderate HL. Nonprogressive. Normal CT scan. Proband has the -103T>C variant in SLC26A4 as well as compound het. variants in USH1C: p.Gly413Alafs*24 and p.(Val472_Gln728del)","Number of Patients":1,"In trans Variants":["p.Gly413Alafs*24","p.(Val472_Gln728del)"],"labels":"eval"},{"CinGen ID":"CA16020850","Variant Name":"NM_000277.3:c.745del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":29288420,"Raw Comment":"PMID: 29288420 - L249fs detected with V388M - reported at Pathogenic in ClinVar (VarID:610, 7 submitters); phase not confirmed - 0.5 points","Number of Patients":"NA","In trans Variants":["p.V388M c.(1162G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA10585393","Variant Name":"NM_000527.5:c.1301C>G","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":29306853,"Raw Comment":"Variant meets PM2 and is identified in 2 siblings from PMID 29306853 with childhood total cholesterol levels >700 mg\/dL and homozygous for this variant. So PM3 is met.","Number of Patients":2,"In trans Variants":["homozygous c.1301C>G p.(Thr434Arg)"],"labels":"eval"},{"CinGen ID":"CA229307","Variant Name":"NM_000277.1:c.1054G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":29316886,"Raw Comment":"Detected with p.Arg243Gln (P- 10 submitters), variable sites in patient genes were aligned with the corresponding sites from the respective parents. PMID: 29316886","Number of Patients":1,"In trans Variants":["p.Arg243Gln c.(728G>A)"],"labels":"eval"},{"CinGen ID":"CA16020812","Variant Name":"NM_000277.3:c.532G>A","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":29316886,"Raw Comment":"Patient 496: IVS4-1G\u00ef\u00bc\u009eA\/p.Glu178Lys. Peripheral blood samples were collected from the patients and parents in each of the 643 core families. To determine sequence variability, variable sites in patient genes were aligned with the corresponding sites from the respective parents.","Number of Patients":1,"In trans Variants":["c.(532G>A) p.Glu178Lys"],"labels":"eval"},{"CinGen ID":"CA16020854","Variant Name":"NM_000277.1:c.755G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":29316886,"Raw Comment":"Detected in trans with p.Arg243Gln (P 10 submitters) variable sites in patient genes were aligned with the corresponding sites from the respective parents. PMID: 29316886","Number of Patients":1,"In trans Variants":["p.Arg243Gln c.(728G>A)"],"labels":"eval"},{"CinGen ID":"CA6748732","Variant Name":"NM_000277.3:c.1174T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":29316886,"Raw Comment":"This variant was detected in trans with the pathogenic variant p.Tyr356* in 2 patients, one was diagnosed with mild hyperphenylalaninemia and the 2nd was diagnosed with classic PKU. This variant was detected in trans with the pathogenic variant p.Arg243Gln in a patient diagnosed with mild hyperphenylalaninemia. This variant was detected in trans with the pathogenic variant p.Ser70del in a patient diagnosed with mild hyperphenylalaninemia. This variant was detected in a second patient diagnosed with classical PKU, however the variant in trans was not reported. Parental analysis was performed to confirm compound heterozygosity.","Number of Patients":5,"In trans Variants":["p.Tyr356* c.(1068C>G)","p.Tyr356* c.(1068C>G)","p.Arg243Gln c.(728G>A)","p.Ser70del"],"labels":"eval"},{"CinGen ID":"CA251535","Variant Name":"NM_000277.3:c.281_283TCA[1]","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":29316886,"Raw Comment":"This variant was documented in one Han Chinese patient diagnosed with mild PKU who was a compound heterozygote with the p.Cys217Tyr VUS in trans (PMID: 29316886). Parental analysis was performed to confirm heterozygosity.","Number of Patients":1,"In trans Variants":["p.Cys217Tyr c.(650G>A)"],"labels":"eval"},{"CinGen ID":"CA401364293","Variant Name":"NM_000152.5:c.955+1G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":29422078,"Raw Comment":"This variant was found in compound heterozygosity with a pathogenic variant in GAA, c.1438-2A>G, in a patient who meets the ClinGen LSD VCEP's PP4 specifications (PMID 29422078). The phase is unknown. Based on the ClinGen LSD VCEP's specifications, this data was given a total of 0.5 points which meets PM3_Supporting.","Number of Patients":1,"In trans Variants":["c.1438-2A>G"],"labels":"eval"},{"CinGen ID":"CA401363493","Variant Name":"NM_001079804.3:c.796C>A","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":29451150,"Raw Comment":"One patient with a diagnosis of Pompe disease has been reported who is compound heterozygous, phase unknown, for the variant and a variant in GAA that has been classified as pathogenic by the ClinGen LSD VCEP, c.2237G>A (p.Trp746Ter) (PMID: 29451150), 0.5 points (PM3_Supporting).","Number of Patients":1,"In trans Variants":["c.2237G>A (p.Trp746Ter)"],"labels":"eval"},{"CinGen ID":"CA180669","Variant Name":"NM_000260.4:c.2476G>A","Condition":"Usher syndrome","Criterion":"PM3","PMID":29490346,"Raw Comment":"74 Israeli and Palestinian families with Usher syndrome received whole exome sequencing. The p.Ala826Thr variant was identified in the homozygous state in 1 North African Jewish family and one Moroccan Jewish family.","Number of Patients":2,"In trans Variants":["homozygous c.2476G>A p.(Ala826Thr)"],"labels":"fine-tune"},{"CinGen ID":"CA229321","Variant Name":"NM_000277.3:c.1066-14C>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":29499199,"Raw Comment":"This variant was detected with pathogenic PAH variant c.1222C>T. It was not specified whether the patient genotype was homozygous or compound heterozygous for the variant. PMID: 29499199","Number of Patients":"1","In trans Variants":["c.1222C>T p.(Arg408Trp)"],"labels":"fine-tune"},{"CinGen ID":"CA16020891","Variant Name":"NM_000277.3:c.910C>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":29499199,"Raw Comment":"In supplementary table 5. BH4 deficiency ruled out.","Number of Patients":0,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA023446","Variant Name":"NM_000527.5:c.1291G>C","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":29502162,"Raw Comment":"variant meets PM2 and was identified in:\n- index case who is homozygous for the variant and has LDL at least 550mg\/dl (figure 2A in the paper) from PMID 29502162 (Klaus et al. 2018), Germany.\n--- individual is homozygous for variant and has an homozygous phenotype, so PM3 is met","Number of Patients":1,"In trans Variants":["homozygous c.1291G>C p.(Ala431Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA274311","Variant Name":"NM_000152.4:c.1128_1129delGGinsC","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":29523196,"Raw Comment":"c.1128_1129delGGinsC was found in compound heterozygosity with a pathogenic variant, -32-13T>G, in an individual with late onset Pompe disease. The phase is unknown. No GAA activity data is available,and therefore this data will not be included. The patient is on ERT.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA308743496","Variant Name":"NM_014297.5:c.505+1G>A","Condition":"ethylmalonic encephalopathy","Criterion":"PM3-Supporting","PMID":29526615,"Raw Comment":"Utilized ClinGen SVI v.10 scoring guidelines for PM3 TOTAL = 0.5 (Homozygote confirmed in trans; PMID 29526615). Unable to count patient O in Tiranti et al 2004 as this was a singleton case","Number of Patients":1,"In trans Variants":["homozygous c.505+1G>A "],"labels":"fine-tune"},{"CinGen ID":"CA400032596","Variant Name":"NM_000212.3:c.1814G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29615672,"Raw Comment":"The patient in PMID: 29615672 is compound heterozygous for Gly605Asp and Asn470Ter (classified Pathogenic by the PD-EP). Confirmation of trans phase was not reported (0.5pt; PM3_supporting).","Number of Patients":1,"In trans Variants":["p.Asn470Ter"],"labels":"eval"},{"CinGen ID":"CA399805155","Variant Name":"NM_000419.5:c.799+2T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"GT17a of PMID: 29675921 is compound heterozygous for Gln891Ter (classified Pathogenic by the PD-EP) and c.799+2C>T. Confirmation of trans phase is not reported. 0.5pt","Number of Patients":1,"In trans Variants":["p.Gln891Ter c.(2671C>T)"],"labels":"others"},{"CinGen ID":"CA8602626","Variant Name":"NM_000419.4:c.2671C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":29675921,"Raw Comment":"3 homozygous probands (GT 4, GT 17b, and GT18) in this article; this exceeds a score of 1.0; therefore, PM3 is met. Additionally, GT26 is compound heterozygous for pathogenic variant Gln778Pro and Gln891Ter and GT 17a is compound heterozygous for Gln891Ter and c.799+2C>T (not yet evaluated by the ClinGen Platelet Disorders VCEP). The variants are not confirmed in trans.","Number of Patients":4,"In trans Variants":["p.Gln778Pro c.(2333A>C)","p.Gln891Ter c.(2671C>T)","c.799+2C>T"],"labels":"others"},{"CinGen ID":"CA399805123","Variant Name":"NM_000419.5:c.812C>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"This variant has been detected in at least 2 individuals with Glanzmann thrombasthenia. Patient GT6 of PMID: 29675921 is compound heterozygous for Ala271Gly and Met724Ile (classified Likely Pathogenic) by the PD VCEP). Confirmation of trans phase was not reported 0.25pt Patient 436 of the GT database is compound heterozygous for Ala271Gly and Tyr220Cys (classified Likely Pathogenic by the PD VCEP). Confirmation of trans phase was not reported 0.25pt Total: 0.5pt (PM3_supporting)","Number of Patients":2,"In trans Variants":["p.Met724Ile c.(2172G>T) c.(2172G>C) c.(2172G>A)"],"labels":"others"},{"CinGen ID":"CA399801004","Variant Name":"NM_000419.5:c.1993C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"GT37 of PMID: 29675921 is reported homozygous for Gln665Ter 0.5pt (PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1993C>T p.(Gln665*)"],"labels":"others"},{"CinGen ID":"CA399798895","Variant Name":"NM_000419.5:c.2172G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"This variant has been detected in at least 2 individuals with Glanzmann thrombasthenia. Patient GT6 of PMID: 29675921 is compound heterozygous for Met724Ile and Ala271Gly (classified Likely Pathogenic by the PD VCEP). Confirmation of trans phase was not reported, not included here to avoid circularity 0pt Patient 440 of the GT database is homozygous for Met724Ile 0.5pt Total: 0.5pt (PM3 _supporting)","Number of Patients":1,"In trans Variants":["p.Ala271Gly c.(812C>G)"],"labels":"others"},{"CinGen ID":"CA399805484","Variant Name":"NM_000419.5:c.659A>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"This variant has been detected in at least 2 individuals with Glanzmann thrombasthenia. Patient GT35 of PMID: 29675921 is compound heterozygous for Tyr220Cys and c.625-1G>A (classified Pathogenic by the PD-EP). Confirmation of trans phase was not reported 0.5pt Patient 436 is compound heterozygous for Tyr220Cys and Ala271Gly (classified VUS by the PD-EP). Confirmation of trans phase was not reported, not considered here to avoid circularity 0pt. Total: 0.5pt (PM3_supporting)","Number of Patients":2,"In trans Variants":["c.625-1G>A","p.Ala271Gly c.(812C>G)"],"labels":"others"},{"CinGen ID":"CA399798124","Variant Name":"NM_000419.4:c.2267+1G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"GT-16 is a compound heterozygous individual with the other variant being pathogenic Gln778Pro.","Number of Patients":1,"In trans Variants":["p.Gln778Pro c.(2333A>C)"],"labels":"others"},{"CinGen ID":"CA915940253","Variant Name":"NM_000212.3:c.1728del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"GT28 of PMID: 29675921 is compound heterozygous for c.1728del and Gln298Ter (Classified Pathogenic by the PD-VCEP). Confirmation of trans phase was not reported. 0.5pt (PM3_supporting).","Number of Patients":1,"In trans Variants":["p.Gln298Ter c.(892C>T)"],"labels":"others"},{"CinGen ID":"CA399800002","Variant Name":"NM_000419.5:c.2029G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"GT1 of PMID: 29675921 is compound heterozygous for Glu677Lys and Arg351Ter (classified Pathogenic by the PD-EP). Confirmation of trans phase was not reported. 0.5pt\t","Number of Patients":1,"In trans Variants":["p.Arg351Ter c.(1051C>T)"],"labels":"others"},{"CinGen ID":"CA8603182","Variant Name":"NM_000419.4:c.1234G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Strong","PMID":29675921,"Raw Comment":"Patient GT19 is homozygous (without parental consanguinity) for the c.1234G>A (p.Gly412Arg) variant. 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.1234G>A p.(Gly412Arg)"],"labels":"others"},{"CinGen ID":"CA915940255","Variant Name":"NM_000212.3:c.1784_1802delinsGTCACA","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"GT41 of PMID: 29675921 is compound heterozygous for c.1784_1802delinsGTCACA and Trp579Ter (classified Pathogenic by the PD-VCEP). Confirmation of trans phase was not reported. 0.5pt\t","Number of Patients":1,"In trans Variants":["p.Trp579Ter c.(1736G>A) c.(1737G>A)"],"labels":"others"},{"CinGen ID":"CA400033923","Variant Name":"NM_000212.3:c.2147G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"GT23 of PMID: 29675921 is compound heterozygous for Gly716Val and Tyr660Ter (classified Pathogenic by the PD-VCEP). Confirmation of trans phase was no reported. 0.5pt\t(PM3_supporting).","Number of Patients":1,"In trans Variants":["p.Tyr660Ter c.(1980C>G) c.(1980C>A)"],"labels":"others"},{"CinGen ID":"CA915940256","Variant Name":"NM_000212.3:c.1300del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"GT42 of PMID: 29675921 is reported homozygous for c.1300del 0.5pt\t(PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1300del p.(Gln434Argfs*9)"],"labels":"others"},{"CinGen ID":"CA123244","Variant Name":"NM_000212.2:c.1199G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":29675921,"Raw Comment":"Patient 34 of the GT database (and PMID:87814) is homozygous for Cys400Tyr 0.5pt GT15a of . PMID: 29675921 is compound heterozygous for Cys400Tyr and c.1525del (classified Pathogenic by the PD-VCEP). Confirmation of trans phase was not reported 0.5pt Total: 1pt (PM3).","Number of Patients":2,"In trans Variants":["p.Cys400Tyr c.(1199G>A)","c.1525del p.(Gln509Argfs*160)"],"labels":"others"},{"CinGen ID":"CA8603457","Variant Name":"NM_000419.4:c.460_462del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":29675921,"Raw Comment":"Patient GT32 (described in supplemental tables 1 and 2) is homozygous for c.460_462del (p.Glu154del). Parental consanguinity is reportedly absent. 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.460_462del p.(Glu154del)"],"labels":"others"},{"CinGen ID":"CA8814791","Variant Name":"NM_000152.3:c.118C>T","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":29869463,"Raw Comment":"Patient CD_7 is compound heterozygous for c.188C>T and c.2015G>A, p.(Arg672Gln). The phase of the variants is unknown. The patient has reduced GAA activity but the level is not available.","Number of Patients":1,"In trans Variants":["c.2015G>A, p.(Arg672Gln)"],"labels":"eval"},{"CinGen ID":"CA229543","Variant Name":"NM_000277.2:c.440C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":30050108,"Raw Comment":"From supplemental table: patient genotype p.P147L\/c.611A>G (p.EX6-96A>G). The validation tests on parents were performed using Sanger sequencing.","Number of Patients":1,"In trans Variants":["c.611A>G p.EX6-96A>G"],"labels":"others"},{"CinGen ID":"CA267693","Variant Name":"NM_000277.2:c.505C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":30050108,"Raw Comment":"Two compound heterozygotes were reported. One patient with Arg169Cys and Arg243Gln (ClinVar 591, Pathogenic) and another with Arg169Cys and Arg408Gln (ClinVar 577, Pathogenic). Parents were tested to confirm carrier status.","Number of Patients":2,"In trans Variants":["p.Arg169Cys c.(505C>T)","p.Arg243Gln c.(728G>A)","p.Arg169Cys c.(505C>T)","p.Arg408Gln c.(1223G>A)"],"labels":"others"},{"CinGen ID":"CA6748732","Variant Name":"NM_000277.3:c.1174T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":30050108,"Raw Comment":"This variant was documented in 7 Chinese patients diagnosed with mild hyperphenylalaninemia. The reported variant in trans for each of the patients was the pathogenic variant c.1197A>T (in 2 patients), the pathogenic variant c.728G>A (p.Arg243Gln) (in 1 patient), the pathogenic variant c.721C>T (in 1 patient), the VUS c.1099C>G (in 1 patient), c.763T>G (in 1 patient), and c.460T>C (in 1 patient). Parental analysis was performed to confirm compound heterozygosity.","Number of Patients":7,"In trans Variants":["c.1197A>T p.(=)","c.728G>A (p.Arg243Gln)","c.721C>T p.(Arg241Cys)","c.1099C>G p.(Leu367Val)","c.763T>G p.(Leu255Val)","c.460T>C p.(Tyr154His)"],"labels":"others"},{"CinGen ID":"CA6748885","Variant Name":"NM_000277.1:c.668A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":30050108,"Raw Comment":"detected in trans with p.Y166* (P 2 submitters) The validation tests on parents were performed. PMID: 30050108","Number of Patients":1,"In trans Variants":["p.Y166\\*"],"labels":"others"},{"CinGen ID":"CA229546","Variant Name":"NM_000277.3:c.441+3G>C","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":30050108,"Raw Comment":"This variant was documented in two patients homozygous for this c.441+3G>C variant, one diagnosed with mild PKU and one diagnosed with classic PKU. This variant was documented in 2 patients with classic PKU, with the pathogenic c.442-1G>A variant in trans. This variant was documented in 1 patient with classic PKU with the p.EX6-96A>G variant in trans. This variant was documented in 1 patient with mild PKU and 1 patient with classic PKU, both with the pathogenic p.Arg243Gln variant in trans. This variant was documented in 1 patient with mild PKU, with the pathogenic p.Arg241Cys variant in trans. This variant was documented in 1 patient with mild PKU with the pathogenic p.Arg408Gln variant in trans. Validation tests on parents were performed using Sanger sequencing.","Number of Patients":5,"In trans Variants":["p.EX6-96A>G","p.Arg243Gln c.(728G>A)","p.Arg241Cys c.(721C>T)","p.Arg408Gln c.(1223G>A)"],"labels":"others"},{"CinGen ID":"CA229801","Variant Name":"NM_000277.2:c.832A>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":30050108,"Raw Comment":"detected in homozygous state in 1 patient. validation tests on parents were performed using Sanger sequencing. 0.5 pts. PMID: 30050108","Number of Patients":1,"In trans Variants":["homozygous c.832A>G p.(Thr278Ala)"],"labels":"others"},{"CinGen ID":"CA16020934","Variant Name":"NM_000277.1:c.1076C>T","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":30050108,"Raw Comment":"2 patients with p.T278I (P 2 submitters)\/p.S359L The validation tests on parents were performed using Sanger sequencing. PMID: 30050108","Number of Patients":2,"In trans Variants":["p.T278I c.(833C>T)","p.S359L c.(1076C>T)"],"labels":"others"},{"CinGen ID":"CA229696","Variant Name":"NM_000277.2:c.694C>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":30050108,"Raw Comment":"Patient genotype: c.442-1G>A (VarID594, P)\/p.Q232*","Number of Patients":1,"In trans Variants":["c.442-1G>A"],"labels":"others"},{"CinGen ID":"CA16020837","Variant Name":"NM_000277.1:c.680T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":30050108,"Raw Comment":"Detected with p.EX6-96A>G. The validation tests on parents were performed using Sanger sequencing. PMID: 30050108","Number of Patients":1,"In trans Variants":["p.EX6-96A>G"],"labels":"others"},{"CinGen ID":"CA16020952","Variant Name":"NM_000277.1:c.1159T>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":30050108,"Raw Comment":"Detected in trans with p.Y356* (P 7 submitters), p.R413P (P 6 submitters), p.R261Q (P 11 submitters). The validation tests on parents were performed using Sanger sequencing. PMID: 30050108","Number of Patients":3,"In trans Variants":["p.Y356* c.(1068C>G)","p.R413P c.(1238G>C)","p.R261Q c.(782G>A)"],"labels":"others"},{"CinGen ID":"CA16020942","Variant Name":"NM_000277.3:c.1115C>G","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":30050108,"Raw Comment":"Detected in trans with p.R176* (2 patients, P 9 submitters), and p.R408W (P 17 submitters). The validation tests on parents were performed using Sanger sequencing. PMID: 30050108","Number of Patients":2,"In trans Variants":["p.R176* c.(526C>T)","p.R408W c.(1222C>T)"],"labels":"others"},{"CinGen ID":"CA253314","Variant Name":"NM_000441.1:c.-103T>C","Condition":"Pendred syndrome","Criterion":"PM3","PMID":30068397,"Raw Comment":"Of 88 unrelated individuals with prelingual nonsyndromic hearing loss, the -103T>C variant was observed in trans with a -66C>G variant in SLC26A4. The proband did not have any GJB2 or MT-RNR1 variants detected.","Number of Patients":1,"In trans Variants":["-66C>G p.(=)"],"labels":"eval"},{"CinGen ID":"CA915940605","Variant Name":"NM_000212.3:c.2031_2041del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":30078718,"Raw Comment":"Patient 2 of PMID: 30078718 is homozygous for the variant (PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.2031_2041del p.(Asp677Glufs*4)"],"labels":"fine-tune"},{"CinGen ID":"CA273892","Variant Name":"NM_000152.3:c.1933G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":30105547,"Raw Comment":"Patient 7 had a diagnosis of hypertrophic cardiomyopathy (HCM) and underwent genetic testing by HCM next generation sequencing panel. This patient is compound heterozygous for c.1933G>A (p.Asp645Asn) and c.794delG (p.Ser265Ilefs*3). No GAA activity is available and therefore this data will not be included.","Number of Patients":1,"In trans Variants":["c.794delG p.Ser265Ilefs*3"],"labels":"fine-tune"},{"CinGen ID":"CA399805999","Variant Name":"NM_000419.5:c.432G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":30138987,"Raw Comment":"Patient in PMID: 30138987 is reported homozygous for Trp144Ter 0.5pt\t","Number of Patients":1,"In trans Variants":["homozygous c.432G>A p.(Trp144*)"],"labels":"fine-tune"},{"CinGen ID":"CA273892","Variant Name":"NM_000152.3:c.1933G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":30155607,"Raw Comment":"Patient 21 is compound heterozygous for c.1933G>A (p.Asp645Asn) and c.2584G>A (p.Gly862Arg). The phase of the variants is unknown. No details on residual GAA activity are available and therefore this data will not be included.","Number of Patients":1,"In trans Variants":["c.2584G>A p.Gly862Arg"],"labels":"fine-tune"},{"CinGen ID":"CA274281","Variant Name":"NM_000152.3:c.1548G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":30155607,"Raw Comment":"Patient #6 is compound heterozygous for c.1548G>A (p.Trp516Ter) and c.-32-13T>G. The phase of the variants is unknown. The diagnosis was confirmed by enzyme assay in fibroblasts, lymphocytes or leukocytes.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA386295865","Variant Name":"NM_001354304.2:c.707-1G>C","Condition":"phenylketonuria","Criterion":"PM3","PMID":30159852,"Raw Comment":"[c.441+5G>T; c.707-1G>C]. Segregation analysis was done. PMID: 30159852","Number of Patients":"NA","In trans Variants":["c.441+5G>T"],"labels":"fine-tune"},{"CinGen ID":"CA386304277","Variant Name":"NM_001354304.2:c.169-1G>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":30159852,"Raw Comment":"[c.169-1G>A; c.168+5G>C] and [c.169-1G>A; c.169-1G>A]. Segregation analysis was done. PMID: 30159852","Number of Patients":2,"In trans Variants":["c.169-1G>A","c.168+5G>C"],"labels":"fine-tune"},{"CinGen ID":"CA397723077","Variant Name":"NM_000018.4:c.515T>C","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Supporting","PMID":30194637,"Raw Comment":"This variant has been detected in at least 2 individuals with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. Of those individuals, 1 was compound heterozygous for the variant and a distinct pathogenic variant. The case was not confirmed in trans by parental or other testing methods. The other variant in this case was c.1332+2T>A, 0.5 points were applied to arrive at PM3_supporting. (PMID 30194637). \n","Number of Patients":2,"In trans Variants":["c.1332+2T>A"],"labels":"fine-tune"},{"CinGen ID":"CA10585649","Variant Name":"NM_000527.5:c.1845+15C>A","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":30269829,"Raw Comment":"Variant meets PM2 and is identified in an index case published in PMID: 30269829 with homozygous FH phenotype (LDL-C = 14.5 mmol\/l) and also duplication of whole PCSK9 gene, classified as Pathogenic by the general ACMG guidelines.","Number of Patients":1,"In trans Variants":["homozygous c.1845+15C>A "],"labels":"fine-tune"},{"CinGen ID":"CA122854","Variant Name":"NM_000536.4:c.686G>A","Condition":"recombinase activating gene 2 deficiency","Criterion":"PM3","PMID":30307608,"Raw Comment":"Five patients (14\u00e2\u0080\u009318) were homozygous for the variant (reaching the maximum 1 pt) PM3_Moderate (PMID: 30307608).\t","Number of Patients":5,"In trans Variants":["NA"],"labels":"fine-tune"},{"CinGen ID":"CA399792888","Variant Name":"NM_000419.5:c.2702C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":30325339,"Raw Comment":"This variant has been detected in at least 3 probands with Glanzmann thrombasthenia. Three probands were reportedly unrelated from different parts of Tunisia and were homozygous for the variant (PMID: 30325339. Total points: 1) (PM3).","Number of Patients":3,"In trans Variants":["homozygous c.2702C>A p.(Ser901*)"],"labels":"fine-tune"},{"CinGen ID":"CA220403","Variant Name":"NM_000152.5:c.2544del","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":30363678,"Raw Comment":"One patient with Pompe disease is compound heterozygous for the variant and a pathogenic variant in GAA, c.-32-13T>G, phase unknown (PMID: 30363678)(0.5 points, PM3_Supporting). Another patient has been reported (doi:10.1186\/1471-2474-14-S2-P3) who is compound heterozygous for the variant and a \"complex deletion\". Because details of the complex deletion are unavailable, this data was not included for PM3.","Number of Patients":2,"In trans Variants":["c.-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA481333203","Variant Name":"NM_001354304.2:c.285C>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":30459323,"Raw Comment":"p.[I95I];[Y204C]. Segregation analysis was not done, so phase is unknown. PMID: 30459323","Number of Patients":"NA","In trans Variants":["p.Y204C c.(611A>G)"],"labels":"eval"},{"CinGen ID":"CA234050","Variant Name":"NM_000152.4:c.1841C>A","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":30564623,"Raw Comment":"Patient AOP13, with a prior clinical diagnosis of limb girdle muscular dystrophy, is compound heterozygous for c.1841C>A (p.Thr614Lys) and c.-32-13T>G. No individual GAA activity is provided, therefore this data will not be included.","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA213717","Variant Name":"NM_000162.5:c.1136C>A","Condition":"monogenic diabetes","Criterion":"PM3","PMID":30592380,"Raw Comment":"This variant has been detected in an individual with neonatal diabetes. This individual was compound heterozygous for the variant and a pathogenic variant and was confirmed in trans by parental\/family testing (PMID 30592380).","Number of Patients":"err","In trans Variants":["p.R191W c.(571C>T)"],"labels":"eval"},{"CinGen ID":"CA8623443","Variant Name":"NM_000212.2:c.2113del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":30792900,"Raw Comment":"At least four homozygous probands have been reported (PMID: 30792900). An additional three compound heterozygotes have not been included here to avoid circularity.","Number of Patients":4,"In trans Variants":["homozygous c.2113del p.(Leu705Cysfs*4)","homozygous c.2113del p.(Leu705Cysfs*4)","homozygous c.2113del p.(Leu705Cysfs*4)","homozygous c.2113del p.(Leu705Cysfs*4)"],"labels":"eval"},{"CinGen ID":"CA915940789","Variant Name":"NM_000419.5:c.1616_1620delinsGGCAC","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":30792900,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia (GT_43 in PMID: 30792900). This individual was homozygous for the variant (0.5 points, PM3_Supporting). \n\n\n","Number of Patients":1,"In trans Variants":["homozygous c.1616_1620delinsGGCAC p.(Leu539_Gln540delinsArgHis)"],"labels":"eval"},{"CinGen ID":"CA400021960","Variant Name":"NM_000212.3:c.437T>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":30792900,"Raw Comment":"This variant has been observed in homozygosity in one individual (Patient GT-76, PMID: 30792900), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.437T>C p.(Leu146Pro)"],"labels":"eval"},{"CinGen ID":"CA915940251","Variant Name":"NM_000419.5:c.1210+5G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":30792900,"Raw Comment":"This variant has been observed in homozygosity in one proband (GT-01, PMID: 30792900), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1210+5G>A"],"labels":"eval"},{"CinGen ID":"CA400034626","Variant Name":"NM_000212.3:c.2302-1G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":30792900,"Raw Comment":"This variant has been observed in homozygosity in one individual (Patient GT-21, PMID: 30792900), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.2302-1G>A"],"labels":"eval"},{"CinGen ID":"CA400032647","Variant Name":"NM_000212.3:c.1835G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":30792900,"Raw Comment":"This variant has been observed in homozygosity in one proband (GT-27, PMID: 30792900), sufficient to apply PM3_supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1835G>A p.(Cys612Tyr)"],"labels":"eval"},{"CinGen ID":"CA229626","Variant Name":"NM_000277.3:c.561G>C","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":30829006,"Raw Comment":"detected with V388M (P by 6 submitters) in Brazilian siblings, parental analysis not reported PMID: 30829006. Genotype not reported for Japanese patient.","Number of Patients":2,"In trans Variants":["p.V388M c.(1162G>A)"],"labels":"eval"},{"CinGen ID":"CA915940222","Variant Name":"NM_000212.3:c.401del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. This proband\nwas homozygous for the variant (PMID: 31029159). Total points: 0.5 points (PM3_Supporting).\n","Number of Patients":1,"In trans Variants":["homozygous c.401del p.(Glu134Glyfs*10)"],"labels":"eval"},{"CinGen ID":"CA915940223","Variant Name":"NM_000419.5:c.1899del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. One proband was homozygous for the variant (PMID:31029159). Total points: .5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1899del p.(Cys633Trpfs*17)"],"labels":"eval"},{"CinGen ID":"CA915940224","Variant Name":"NM_000419.5:c.409-3C>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"This variant was homozygous in the reported individual (Patient 8, PMID: 31029159) with a clinical diagnosis of GT. Since this was a homozygous occurrence and this variant was not seen in the literature elsewhere; per SVI recommendations this receives 0.5pt since this variant has a MAF of <0.0001 (PM3_Supporting). This variant was identified as heterozygous in parents and not homozygous in healthy individuals in the family.","Number of Patients":1,"In trans Variants":["homozygous c.409-3C>G"],"labels":"eval"},{"CinGen ID":"CA8603504","Variant Name":"NM_000419.5:c.286T>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"This variant was homozygous in the reported individual (Patient 11, PMID: 31029159) with a clinical diagnosis of GT. Since this was a homozygous occurrence and this variant was not seen in the literature elsewhere; per SVI recommendations this receives 0.5pt since this variant has a MAF of <0.0001 (PM3_Supporting). This variant was identified as heterozygous in parents and not homozygous in healthy individuals in the family.","Number of Patients":1,"In trans Variants":["homozygous c.286T>A p.(Cys96Ser)"],"labels":"eval"},{"CinGen ID":"CA399805055","Variant Name":"NM_000419.5:c.842C>T","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"Case 12 of PMID: 31029159 is homozygous for Thr281Ile.","Number of Patients":1,"In trans Variants":["homozygous c.842C>T p.(Thr281Ile)"],"labels":"eval"},{"CinGen ID":"CA915940225","Variant Name":"NM_000419.5:c.1071dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann Thrombasthenia. One proband was homozygous for the variant (PMID:31029159). Total points: .5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1071dup p.(Arg358Alafs*47)"],"labels":"eval"},{"CinGen ID":"CA400028645","Variant Name":"NM_000212.3:c.1303G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann Thrombasthenia. One proband was homozygous for the variant, confirmed via paternal testing (PMID: 31029159). Total points: .5 (PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1303G>T p.(Glu435*)"],"labels":"eval"},{"CinGen ID":"CA500273575","Variant Name":"NM_000419.5:c.1392A>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"This variant was homozygous in the reported individual (Patient 10, PMID: 31029159) with a clinical diagnosis of GT. Since this was a homozygous occurrence and this variant was not seen in the literature elsewhere; per SVI recommendations this receives 0.5pt since this variant has a MAF of <0.0001 (PM3_Supporting). This variant was identified as heterozygous in parents and not homozygous in healthy individuals in the family.","Number of Patients":1,"In trans Variants":["homozygous c.1392A>G p.(=)"],"labels":"eval"},{"CinGen ID":"CA399802559","Variant Name":"NM_000419.5:c.1555C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31029159,"Raw Comment":"This variant has been detected in at least 1 proband with Glanzmann thrombasthenia. One proband was homozygous for the variant (PMID:31029159). Total points: .5 (PM3_Supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1555C>T p.(Gln519*)"],"labels":"eval"},{"CinGen ID":"CA8338033","Variant Name":"NM_000018.4:c.1183-7A>G","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3-Supporting","PMID":31031081,"Raw Comment":"Total points = 0.5; Authors mention that variant is found in trans with pathogenic c.1322G>A p.(G441D); unknown phasing (PMID:31031081).","Number of Patients":1,"In trans Variants":["c.1322G>A p.G441D"],"labels":"fine-tune"},{"CinGen ID":"CA400023678","Variant Name":"NM_000212.2:c.761A>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31064749,"Raw Comment":"This variant has been reported homozygous in one patient in PMID: 31064749.","Number of Patients":1,"In trans Variants":["homozygous c.761A>G p.(Gln254Arg)"],"labels":"fine-tune"},{"CinGen ID":"CA8603420","Variant Name":"NM_000419.5:c.624+5G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31064749,"Raw Comment":"TGP0464 of PMID: 31064749 is compound heterozygous for Asp396Asn (classified Pathogenic by PD-EP) and c.624+5G>A. Phase not confirmed. 0.5pt","Number of Patients":1,"In trans Variants":["p.Asp396Asn c.(1186G>A)"],"labels":"fine-tune"},{"CinGen ID":"CA915940799","Variant Name":"NM_000419.5:c.2883del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31064749,"Raw Comment":"Patient TGP0086 (PMID: 31064749) is homozygous for this variant.","Number of Patients":1,"In trans Variants":["homozygous c.2883del p.(Phe961Leufs*?)"],"labels":"fine-tune"},{"CinGen ID":"CA626224613","Variant Name":"NM_000419.5:c.559del","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":31064749,"Raw Comment":"Patient TGP0121 of PMID: 31064749 is homozygous.","Number of Patients":1,"In trans Variants":["homozygous c.559del p.(Val187Trpfs*37)"],"labels":"fine-tune"},{"CinGen ID":"CA400028942","Variant Name":"NM_000212.2:c.1366A>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3-Supporting","PMID":31064749,"Raw Comment":"This variant has been reported homozygous once in the literature (PMID: 31064749 Patient TGP0361). 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.1366A>C p.(Thr456Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA500651166","Variant Name":"NM_000212.3:c.1409dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31064749,"Raw Comment":"GT patient TGP0028 (PMID: 31064749) is homozygous for this variant 0.5pt\t(PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.1409dup p.(Asn470Lysfs*2)"],"labels":"fine-tune"},{"CinGen ID":"CA915940803","Variant Name":"NM_000212.3:c.55dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":31064749,"Raw Comment":"This variant has been detected in at least 1 proband with type 1 Glanzmann thrombasthenia. One probands was homozygous for the variant (PMID:31064749, Total points: .5 points (PM3_supporting).\n","Number of Patients":1,"In trans Variants":["homozygous c.55dup p.(Ala19Glyfs*36)"],"labels":"fine-tune"},{"CinGen ID":"CA400023674","Variant Name":"NM_000212.3:c.760C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":31088191,"Raw Comment":"Proband 2 of PMID: 31088191 is compound heterozygous for the paternal Cys549Ser (classified Likely Pathogenic by the PD-VCEP) and maternal Gln254Lys variants. 1pt","Number of Patients":1,"In trans Variants":["p.Gln254Lys c.(760C>A)","p.Cys549Ser c.(1645T>A)"],"labels":"fine-tune"},{"CinGen ID":"CA400030198","Variant Name":"NM_000212.3:c.1646G>C","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":31088191,"Raw Comment":"At least 2 compound heterozygous individuals have been reported with this variant in PMID: 31088191 confirmed in trans with c.2113del (Pathogenic, 1pt) and Gln254Lys (Likely Pathogenic; not included here to avoid circularity) respectively.","Number of Patients":2,"In trans Variants":["p.Gln254Lys c.(760C>A)","c.2113del p.(Leu705Cysfs*4)"],"labels":"fine-tune"},{"CinGen ID":"CA913191009","Variant Name":"NM_000152.5:c.1952del","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":31125121,"Raw Comment":"Two adult siblings are reported to be compound heterozygous for the variant ((labeled as c.1951del in the publication) and a pathogenic variant in GAA, c.-32-13T>G; phase unknown (PMID: 31125121), 0.5 points (PM3_Supporting).","Number of Patients":2,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA172206","Variant Name":"NM_004004.5:c.101T>C","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Very Strong","PMID":31160754,"Raw Comment":"This study showed that the p.Met34Thr variant occurred in 27 homozygous probands, 17 times in trans with the p.Val37Ile variant, 138 times in trans with a P\/LP variant and 78 times in trans with a premature termination codon in GJB2. This more than maxes out the PM3_VS points.","Number of Patients":44,"In trans Variants":["homozygous c.101T>C p.(Met34Thr)","p.Val37Ile c.(109G>A)"],"labels":"eval"},{"CinGen ID":"CA172210","Variant Name":"NM_004004.5:c.109G>A","Condition":"nonsyndromic genetic deafness","Criterion":"PM3","PMID":31160754,"Raw Comment":">120 compound hets with the p.V37I variant","Number of Patients":">120","In trans Variants":["p.V37I c.(109G>A)"],"labels":"eval"},{"CinGen ID":"CA6327349","Variant Name":"NM_005422.2:c.4085G>A","Condition":"nonsyndromic genetic deafness","Criterion":"PM3-Supporting","PMID":31163360,"Raw Comment":"Seen in 1 individual who harbored another nonsense variant, p.Tyr1942Ter, in TECTA, classified as pathogenic in ClinVar by EGL (PMID: 31163360). Also seen by LMM in 1 individual who also carried a VUS in TECTA, however no points were applied since the phase was unknown.","Number of Patients":1,"In trans Variants":["p.Tyr1942Ter c.(5826C>A)"],"labels":"fine-tune"},{"CinGen ID":"CA401368920","Variant Name":"NM_001079804.3:c.1670T>G","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":31342611,"Raw Comment":"One patient is compound heterozygous for the variant and c.-32-13T>G, phase unknown (PMID 31342611), 0.5 points (PM3_Supporting).","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"eval"},{"CinGen ID":"CA16020801","Variant Name":"NM_000277.3:c.498C>G","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":31355225,"Raw Comment":"The patient in PMID: 31355225 is homozygous. 0.5pt","Number of Patients":1,"In trans Variants":["homozygous c.498C>G p.(Tyr166*)"],"labels":"fine-tune"},{"CinGen ID":"CA386303850","Variant Name":"NM_000277.3:c.32T>A","Condition":"phenylketonuria","Criterion":"PM3","PMID":31355225,"Raw Comment":"It has been previously reported in one Ugyur proband (PMID: 31355225) with classic PKU; BH4 deficiency was formally excluded by urinary pterin analysis (PP4_Moderate). The patient was compound heterozygous for the variant (confirmed by parental testing) and carried it in trans with the p.R413P variant (known pathogenic per PAH ClinGen working group) (PM3).","Number of Patients":1,"In trans Variants":["p.R413P c.(1238G>C)"],"labels":"fine-tune"},{"CinGen ID":"CA386492936","Variant Name":"NM_000277.3:c.1304A>T","Condition":"phenylketonuria","Criterion":"PM3","PMID":31355225,"Raw Comment":"PMID: 31355225 - Patient 108 carried the previously described variant p.Ala434Asp (VarID 102586, LP, 2 submitters), parents were tested - variants confirmed in trans - 1.0 points","Number of Patients":1,"In trans Variants":["p.Ala434Asp c.(1301C>A)"],"labels":"fine-tune"},{"CinGen ID":"CA386493121","Variant Name":"NM_000277.3:c.1200-2A>C","Condition":"phenylketonuria","Criterion":"PM3-Strong","PMID":31355225,"Raw Comment":"It has been previously reported in two Ugyur probands (PMID: 31355225) with classic PKU; BH4 deficiency was formally excluded by urinary pterin analysis (PP4_Moderate). Both cases were compound heterozygous for the variant (confirmed by parental testing): one carried it in trans with the p.A104D variant (known pathogenic per PAH ClinGen working group) and the other in trans with p.P147L variant (Likely Pathogenic per PAH ClinGen working group) (PM3_Strong).","Number of Patients":2,"In trans Variants":["p.A104D c.(311C>A)","p.P147L c.(440C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA386492907","Variant Name":"NM_000277.3:c.1316-1G>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":31355225,"Raw Comment":"It has been previously reported in seven Ugyur probands (PMID: 31355225): three homozygotes with mild PKU; one compound heterozygote with classic PKU in trans with the p.R413P variant (Pathogenic per ClinGen PAH working group); one compound heterozygote with classic PKU in trans with the p.R243Q variant (Pathogenic per ClinGen PAH working group); one compound heterozygote with mild PKU in trans with the p.A300S variant (Pathogenic per ClinGen PAH working group); and one compound heterozygote with mild PKU in trans with the p.E182K (Likely Pathogenic per ClinGen PAH working group) variant (PM3_VeryStrong).","Number of Patients":7,"In trans Variants":["p.R243Q c.(728G>A)","p.R413P c.(1238G>C)","p.E182K c.(544G>A)","homozygous c.1316-1G>A ","p.A300S c.(898G>T)"],"labels":"fine-tune"},{"CinGen ID":"CA915946683","Variant Name":"NM_000277.3:c.346_347delGA","Condition":"phenylketonuria","Criterion":"PM3","PMID":31355225,"Raw Comment":"It has been previously reported in an Ugyur proband (PMID: 31355225) with mild PKU; BH4 deficiency was formally excluded by urinary pterin analysis (PP4_Moderate). The patient was compound heterozygous for the variant (confirmed by parental testing) and carried it in trans with the p.E390G variant (Likely Pathogenic per ClinGen PAH working group) (PM3).","Number of Patients":1,"In trans Variants":["p.E390G c.(1169A>G)"],"labels":"fine-tune"},{"CinGen ID":"CA913191011","Variant Name":"NM_000152.5:c.2655_2656del","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":31392188,"Raw Comment":"Two siblings with late-onset Pompe disease are compound heterozygous for the variant and c.-32-13T>G, a known pathogenic variant in GAA (PMID 31392188). The phase is unknown. Total 0.5 points (PM3_Supporting).","Number of Patients":2,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA401366794","Variant Name":"NM_000152.5:c.1445C>G","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":31392188,"Raw Comment":"This variant has been detected in 1 individual with Pompe disease. The individual was compound heterozygous for the variant and a pathogenic variant, c.-32-13T>G (PMID: 31392188, 0.5pt). (PM3_Supporting).\n","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA913191010","Variant Name":"NM_000152.5:c.1951_1952delinsT","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":31392188,"Raw Comment":"Two siblings with late onset Pompe disease are compound heterozygous for the variant and a pathogenic variant in GAA, c.-32-13T>G (PMID 31392188) (PP4). In addition, an adult patient with clinical symptoms consistent with Pompe disease, undergoing genetic testing in a clinical laboratory, is compound heterozygous for the variant and another variant in GAA that has been classified as pathogenic by the ClinGen LD VCEP, c.2014C>T (p.Arg672Trp) (clinical laboratory). The phase is unknown in both families (0.5 points per proband = 1 point) (PM3).","Number of Patients":3,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA6748732","Variant Name":"NM_000277.3:c.1174T>A","Condition":"phenylketonuria","Criterion":"PM3-Very Strong","PMID":31445982,"Raw Comment":"This variant was documented in one patient with mild hyperphenylalaninemia with the pathogenic variant c.331C>T (p.Arg111Ter) in trans. Parental analysis was not performed to confirm compound heterozygosity.","Number of Patients":1,"In trans Variants":["c.331C>T p.Arg111Ter"],"labels":"fine-tune"},{"CinGen ID":"CA401367134","Variant Name":"NM_000152.5:c.1538A>G","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":31510962,"Raw Comment":"This variant has been detected as homozygous in one individual with infantile-onset Pompe disease and in one individual with deficient GAA enzyme activity and clinical features of Pompe disease (PM3 1.0 points, PMID 31510962, clinical laboratory data) (PM3).","Number of Patients":2,"In trans Variants":["homozygous c.1538A>G p.(Asp513Gly)","homozygous c.1538A>G p.(Asp513Gly)"],"labels":"eval"},{"CinGen ID":"CA501005","Variant Name":"NM_000152.5:c.1003G>A","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":31510962,"Raw Comment":"This variant has been detected in at least 4 individuals with Pompe disease. Of those individuals, one was compound heterozygous for the variant and a pathogenic or likely pathogenic variant and confirmed in trans by parental\/family testing (c.876C>G p.Tyr292X, PMID 31510962, 1 pt).\n\n","Number of Patients":4,"In trans Variants":["c.876C>G p.Tyr292X","homozygous c.1003G>A p.(Gly335Arg)","homozygous c.1003G>A p.(Gly335Arg)","homozygous c.1003G>A p.(Gly335Arg)"],"labels":"eval"},{"CinGen ID":"CA16041903","Variant Name":"NM_000152.5:c.2242G>T","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":31545528,"Raw Comment":"One patient with late onset Pompe disease is compound heterozygous for the variant and a pathogenic variant in GAA, c.-32-13T>G, phase unknown (PMID: 31545528), 0.5 points (PM3_Supporting).","Number of Patients":1,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA400023389","Variant Name":"NM_000212.2:c.629G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":31565851,"Raw Comment":"The patient is compound heterozygous for Pro189Ser (classified as Pathogenic by the ClinGen Platelet Disorders VCEP) and Cys210Ser . The variants are in trans as confirmed by independent segregation in the next generation (PM3; PMID: 31565851).","Number of Patients":1,"In trans Variants":["p.Pro189Ser c.(565C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229726","Variant Name":"NM_000277.2:c.737C>A","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":31623983,"Raw Comment":"p.R408W parental analysis not reported PMID: 31623983","Number of Patients":1,"In trans Variants":["p.R408W c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA16020960","Variant Name":"NM_001354304.2:c.1199+1G>T","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":31623983,"Raw Comment":"One patient in PMID: 31623983 is compound heterozygous for c.1199+1G>T and Arg408Trp (ClinVar 577, classified Pathogenic by the PAH VCEP), however, investigation of trans phase was not reported (PM3_supporting).","Number of Patients":1,"In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA229394","Variant Name":"NM_000277.2(PAH):c.1200-1delG","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":31623983,"Raw Comment":"One patient in PMID: 31623983 is compound heterozygous for c.1200del and Arg408Trp (ClinVar 577, classified Pathogenic by the PAH VCEP), however, investigation of trans phase was not reported (PM3_supporting).","Number of Patients":1,"In trans Variants":["p.Arg408Trp c.(1222C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA380140584","Variant Name":"NM_000536.4:c.1338C>G","Condition":"recombinase activating gene 2 deficiency","Criterion":"PM3-Supporting","PMID":31973905,"Raw Comment":"PMID: 31973905 reports one homozygous patient, 0.5 pts, PM3_Supporting.","Number of Patients":1,"In trans Variants":["homozygous c.1338C>G p.(Cys446Trp)"],"labels":"fine-tune"},{"CinGen ID":"CA8603305","Variant Name":"NM_000419.4:c.889G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3","PMID":32089034,"Raw Comment":"1 homozygous individual from internal laboratory data, with parents tested and found to be heterozygous for the variant and a second homozygote reported in PMID: 32089034 (1pt; PM3).","Number of Patients":1,"In trans Variants":["homozygous c.889G>C p.(Ala297Pro)"],"labels":"fine-tune"},{"CinGen ID":"CA400031690","Variant Name":"NM_000212.3:c.121C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":32089034,"Raw Comment":"This variant has been detected in at least one homozygous proband with Glanzmann thrombasthenia (PM3_supporting;PMID: 32089034).","Number of Patients":1,"In trans Variants":["homozygous c.121C>T p.(Gln41*)"],"labels":"fine-tune"},{"CinGen ID":"CA2573131753","Variant Name":"NM_000419.5:c.1999dup","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":32089034,"Raw Comment":"This variant has been detected in at least one homozygous proband with Glanzmann thrombasthenia (PM3_supporting; PMID: 32089034).","Number of Patients":1,"In trans Variants":["homozygous c.1999dup p.(Asp667Glyfs*11)"],"labels":"fine-tune"},{"CinGen ID":"CA399804633","Variant Name":"NM_000419.5:c.1021G>A","Condition":"Glanzmann's thrombasthenia","Criterion":"PM3","PMID":32089034,"Raw Comment":"Case 5 of PMID: 32089034 and an additional case from Northern Blood Research Centre, Kolling Institute, at The University of Sydney are both homozygous for Ala341Thr (1pt; PM3).","Number of Patients":1,"In trans Variants":["homozygous c.1021G>A p.(Ala341Thr)"],"labels":"fine-tune"},{"CinGen ID":"CA16020852","Variant Name":"NM_001354304.2:c.750_751del","Condition":"phenylketonuria","Criterion":"PM3-Supporting","PMID":32106880,"Raw Comment":"One compound heterozygous patient has been described (PMID: 32106880) with Arg252GlyfsTer30 and Arg158Trp (ClinVar 102693, Pathogenic reviewed by GCEP). Confirmation of trans phase was not reported.","Number of Patients":1,"In trans Variants":["p.Arg158Trp c.(472C>T)"],"labels":"eval"},{"CinGen ID":"CA400030376","Variant Name":"NM_000212.3:c.1690G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":32237906,"Raw Comment":"This variant has been detected in at least 1 individual with Glanzmann thrombasthenia. GT3 of PMID: 32237906 is compound heterozygous for this variant and a pathogenic variant (c.361+1G>A; 0.5pt). Total points: 0.5 (PM3_Supporting).\n","Number of Patients":1,"In trans Variants":["c.361+1G>A"],"labels":"fine-tune"},{"CinGen ID":"CA923726221","Variant Name":"NM_000212.3:c.756del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":32237906,"Raw Comment":"GT1 of PMID: 32237906 is homozygous for c.756del (0.5pt)","Number of Patients":1,"In trans Variants":["homozygous c.756del p.(Met253Cysfs*30)"],"labels":"fine-tune"},{"CinGen ID":"CA923726222","Variant Name":"NM_000419.5:c.2444_2445del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":32237906,"Raw Comment":"GT16 (PMID: 32237906) is compound heterozygous for c.2444_2445del and Arg977Ter (classified pathogenic by the PD-VCEP). Confirmation of trans phase was not reported. (PM3_supporting)","Number of Patients":1,"In trans Variants":["p.Arg977Ter c.(2929C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA626684825","Variant Name":"NM_000212.3:c.225_226del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":32237906,"Raw Comment":"GT7 (PMID: 32237906) is compound heterozygous for c.225_226del and Arg242Ter (classified Pathogenic by the PD-VCEP). Confirmation of trans phase was not reported.","Number of Patients":1,"In trans Variants":["p.Arg242Ter c.(724C>T)"],"labels":"fine-tune"},{"CinGen ID":"CA9871496","Variant Name":"NM_000022.4:c.845G>A","Condition":"adenosine deaminase deficiency","Criterion":"PM3-Strong","PMID":32307643,"Raw Comment":"PMID: 32307643, Patients 3 and 25, both are homozygous, reaching the maximum of 1 point for homozygous occurrence. From the same report, patient 2: Compound heterozygous,c.221G>T, p.G74V, Likely Pathogenic according to SCID VCEP specifications; 1 point. Total 2 points, PM3_Strong.\t","Number of Patients":3,"In trans Variants":["homozygous c.845G>A p.(Arg282Gln)","homozygous c.845G>A p.(Arg282Gln)","c.221G>T p.G74V"],"labels":"eval"},{"CinGen ID":"CA16620645","Variant Name":"NM_000152.5:c.1062C>A","Condition":"glycogen storage disease II","Criterion":"PM3-Supporting","PMID":32373469,"Raw Comment":"One patient has been identified who is compound heterozygous for the variant and another variant in GAA that has been classified as pathogenic by the ClinGen LD VCEP, c.1935C>A (p.Asp645Glu) (PMID: 32373469), (PM3_Supporting)","Number of Patients":1,"In trans Variants":["c.1935C>A p.Asp645Glu"],"labels":"eval"},{"CinGen ID":"CA397725788","Variant Name":"NM_000018.4:c.1748C>T","Condition":"very long chain acyl-CoA dehydrogenase deficiency","Criterion":"PM3","PMID":32518924,"Raw Comment":"Of those individuals, both were homozygous for the variant (PM3 point 1.0, PMID 32518924) (PM3).","Number of Patients":2,"In trans Variants":["homozygous c.1748C>T p.(Ser583Leu)","homozygous c.1748C>T  p.(Ser583Leu)"],"labels":"eval"},{"CinGen ID":"CA399804688","Variant Name":"NM_000419.5:c.998+1G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":32581362,"Raw Comment":"One homozygous patient has been reported with Glanzmann thrombasthenia (PMID: 32581362; PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.998+1G>C"],"labels":"eval"},{"CinGen ID":"CA8815129","Variant Name":"NM_000152.5:c.1019A>G","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":32802993,"Raw Comment":"This variant has been detected in at least 4 individuals with Pompe disease. Of those\nindividuals, 3 were compound heterozygous for the variant and a pathogenic or likely pathogenic variant and 1 of those were confirmed in trans by parental testing, including c.-32-13T>G (1 patient, internal lab data, confirmed in trans, 1.0 point), c.2560C>T; p.Arg854* (1 patient, internal lab data, phase unknown, 0.5 points), and c.1292_1295dup p.(Gln433Alafs *74) (1 patient, PMID: 32802993, phase unknown and no follow up to NBS, 0 points). In addition, one patient is compound heterozygous for the variant and c.1725C>T (p.Tyr575Tyr) (internal lab data), which is not classified as P\/LP (0 points) and one patient was compound heterozygous for the variant and c.2432delT (p.Leu811Argfs*37) (internal lab data, confirmed in trans), but enzyme testing was in the carrier range (0 points). (1.5 total points, meeting PM3).","Number of Patients":1,"In trans Variants":["c.1292_1295dup p.(Gln433Alafs *74)"],"labels":"eval"},{"CinGen ID":"CA023773","Variant Name":"NM_000527.5:c.828C>A","Condition":"hypercholesterolemia, familial","Criterion":"PM3","PMID":32977124,"Raw Comment":"Variant identified as homozygous state in an index case with homozygous FH phenotype from PMID: 32977124.","Number of Patients":1,"In trans Variants":["homozygous c.828C>A p.(Cys276*)"],"labels":"fine-tune"},{"CinGen ID":"CA247031","Variant Name":"NM_000152.5:c.1194+3G>C","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":33073003,"Raw Comment":"Three patients have been reported who are compound heterozygous for the variant and another variant in GAA that has been classified as pathogenic or likely pathogenic by the ClinGen LSD VCEP, including c.1781G>A (p.Arg594His), LP (mother is heterozygous for c.1781G>A, no paternal testing), 0.5 points (Clinical Laboratory, PMID: 33073003); c.1210G>A (p.Asp404Asn), confirmed in trans, 1 point (Clinical Laboratory), and c.1841C>A (p.Thr614Lys), phase unknown, 0.5 points (Clinical Laboratory. Total 2 points (PM3_Strong).","Number of Patients":3,"In trans Variants":["c.1781G>A (p.Arg594His)","c.1210G>A (p.Asp404Asn)","c.1841C>A (p.Thr614Lys)"],"labels":"eval"},{"CinGen ID":"CA262046","Variant Name":"NM_194248.2(OTOF):c.5193-1G>A","Condition":"nonsyndromic genetic deafness","Criterion":"PM3","PMID":33111345,"Raw Comment":"Found in homozygous family with HL and ANSD (phase unconfirmed; 0.5 PM3 pts; PMID: 33111345). Reported in LMM case compound heterozygous (phase unconfirmed) with c.2370_2371insA (D791fs), a LP var in ClinVar (0.5 PM3 pts). Total PM3 pts = 1.","Number of Patients":2,"In trans Variants":["c.2370_2371insA p.(Asp791Argfs*102)"],"labels":"eval"},{"CinGen ID":"CA16041905","Variant Name":"NM_000152.5:c.2281delinsAT","Condition":"glycogen storage disease II","Criterion":"PM3","PMID":33202836,"Raw Comment":"Two patients are compound heterozygous for the variant and a pathogenic variant in GAA, c.-32-13T>G, phase unknown (2 x 0.5 points = 1 point, PM3). Another patient was identified by newborn screening and was compound heterozygous for the variant, c.2238G>C (p.Trp746Cys), and a pseudodeficiency variant, c.2065G>A (PMID 33202836). This data may be used in the assessment of p.Trp746Cys and was not included here to avoid circular logic.","Number of Patients":3,"In trans Variants":["c.-32-13T>G","c.2238G>C p.(Trp746Cys)"],"labels":"eval"},{"CinGen ID":"CA8815361","Variant Name":"NM_000152.5:c.1537G>A","Condition":"glycogen storage disease II","Criterion":"PM3-Strong","PMID":33301762,"Raw Comment":"This variant has been detected as homozygous in one individual with late-onset Pompe disease, and as compound heterozygous with the pathogenic c.-32-13T>G variant in three siblings with deficient GAA enzyme activity (PM3 2.0 points, PMID 33301762, Duke University Molecular Diagnostics Laboratory) (PM3_Strong).","Number of Patients":3,"In trans Variants":["c.-32-13T>G"],"labels":"fine-tune"},{"CinGen ID":"CA400029054","Variant Name":"NM_000212.3:c.1388G>C","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":34267460,"Raw Comment":"Patient 7 of PMID: 34267460 is homozygous for this variant (0.5pt; PM3_supporting).\t","Number of Patients":1,"In trans Variants":["homozygous c.1388G>C p.(Cys463Ser)"],"labels":"fine-tune"},{"CinGen ID":"CA399794330","Variant Name":"NM_000419.5:c.2578C>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":34267460,"Raw Comment":"Patient 6 of PMID: 34267460 is homozygous for this variant (0.5pt; PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.2578C>T p.(Gln860*)"],"labels":"fine-tune"},{"CinGen ID":"CA399805900","Variant Name":"NM_000419.5:c.476G>T","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":34275420,"Raw Comment":"P2 (PMID: 34275420) is homozygous for this variant (PM3_supporting).","Number of Patients":1,"In trans Variants":["homozygous c.476G>T p.(Gly159Val)"],"labels":"fine-tune"},{"CinGen ID":"CA400030168","Variant Name":"NM_000212.3:c.1641C>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":34275420,"Raw Comment":"P18 is homozygous for this variant (PMID: 34275420; PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.1641C>A p.(Cys547*)"],"labels":"fine-tune"},{"CinGen ID":"CA399795789","Variant Name":"NM_000419.5:c.2444A>G","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":34275420,"Raw Comment":"P15 is homozygous for this variant (PMID: 34275420; PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.2444A>G p.(Tyr815Cys)"],"labels":"fine-tune"},{"CinGen ID":"CA1139665644","Variant Name":"NM_000419.5:c.2975_2979del","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":34275420,"Raw Comment":"P16 is homozygous for this variant (PMID: 34275420; PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.2975_2979del p.(Glu992Glyfs*42)"],"labels":"fine-tune"},{"CinGen ID":"CA399803524","Variant Name":"NM_000419.5:c.1361G>A","Condition":"Glanzmann thrombasthenia","Criterion":"PM3-Supporting","PMID":34275420,"Raw Comment":"P3 (PMID: 34275420) is homozygous for this variant. 0.5pt (PM3_supporting)","Number of Patients":1,"In trans Variants":["homozygous c.1361G>A p.(Gly454Asp)"],"labels":"fine-tune"},{"CinGen ID":"CA182451","Variant Name":"NM_194248.3:c.5374C>T","Condition":"nonsyndromic genetic deafness","Criterion":"PM3","PMID":34416374,"Raw Comment":"This variant has been detected in at least 3 individuals with AR deafness. For two of those individuals, both were compound heterozygous for the variant and a VUS meeting PM2_Supporting, and both of those were confirmed in trans by family testing (c.2676G>A (p.K892K) which occurs at the last nucleotide in exon (22) of OTOF and c.4748G>A (p.R1583H), 1.5 PM3 points, PMID: 34416374, Universit\u00c3\u00a4tsmedizin G\u00c3\u00b6ttingen, Institute of Human Genetics\/Institute of Auditory Neuroscience & InnerEarLab) (PM3).","Number of Patients":3,"In trans Variants":["c.2676G>A p.K892K","c.4748G>A p.R1583H"],"labels":"fine-tune"},{"CinGen ID":"CA376065642","Variant Name":"NM_001033855.3:c.95C>G","Condition":"severe combined immunodeficiency due to DCLRE1C deficiency","Criterion":"PM3-Supporting","PMID":35886058,"Raw Comment":"The patient reported in Rosina E et al. is homozygous for this variants. 0.5 pts, PM3_Supporting (PMID: 35886058).","Number of Patients":1,"In trans Variants":["homozygous c.95C>G p.(Ser32Cys)"],"labels":"eval"},{"CinGen ID":"CA376060149","Variant Name":"NM_001033855.3:c.406G>A","Condition":"severe combined immunodeficiency due to DCLRE1C deficiency","Criterion":"PM3-Strong","PMID":36546626,"Raw Comment":"2 patients reported. 1) This variant identified in 1 white\/Causasian patient at Invitae with clinical diagnosis of SCID meeting PP4 criteria. Variant heterozygous, co-occurs in trans with c.629del (p.Tyr210Leufs*14). Variants confirmed in trans via parental testing. No alternate cause for disease identified, 407 gene immunodeficiency panel ordered which included all known SCID genes. The co-occurring variant c.629del (p.Tyr210Leufs*14) is absent from gnomAD (PM2) and is a frameshift variant occurring in exon 8 out of 14 (PVS1 - frameshift variant predicted to undergo NMD in a LOF gene). PM2 + PVS1 alone is enough to classify c.629del (p.Tyr210Leufs*14) as LP, but we also additionally can apply PP4 to the variant as well. Therefore, the co-occurring variant is at least LP and is confirmed in trans with our variant in this patient. This is worth 1 point under SVI recommendation for PM3. 2) This variant identified in 1 while\/Caucasian patient in PMID: 36546626 (ART007) meeting PP4 criteria. Variant co-occurs with Deletion (Exons 1-5). Inclusion criteria for cohort reported in this paper included that patient must have mutation of both alleles, therefore the variants are in trans. Deletion (Exons 1-5) has not yet been interpreted by the SCID VCEP, but this variant would be at least LP since it is a CNV that deletes the first 5 exons of the gene, which would include the initiator codon and several missense variants located in this region have been classified as LP or P by the SCID VCEP (p.Ile16Thr and p.Thr65Ile for example). Adding 1 point for in trans with LP\/P for patient ART007. Therefore between these 2 patients we have 2 points total and PM3_Strong can be applied to our variant.","Number of Patients":1,"In trans Variants":["Deletion (Exons 1-5)"],"labels":"eval"},{"CinGen ID":"CA376061171","Variant Name":"NM_001033855.3:c.346T>C","Condition":"severe combined immunodeficiency due to DCLRE1C deficiency","Criterion":"PM3","PMID":36546626,"Raw Comment":"ART012 (PMID: 36546626): Variant co-occurs with c.161+2T>G. This variant has not yet been classified by the SCID VCEP but it is absent gnomAD (PM2_Supporting) and is a +1\/+2 splice dinucleotide variant expected to result in out of frame exon skipping (NMD+) in a LOF gene, which would qualify for PVS1. PVS1 + PM2_Supproting is enough to classify variant as Likely Pathogenic. While phase of the variants is not clear from main text, the inclusion criteria in supplemental file indicates that for inclusion mutation of both alleles must be present. Therefore variants would be in trans. 1 point for in trans with LP\/P variant. PM3 is met at regular strength.","Number of Patients":"1","In trans Variants":["c.161+2T>G"],"labels":"eval"}]
\ No newline at end of file
diff --git a/PM3-Bench/README.md b/PM3-Bench/README.md
index e69de29..f1978a0 100644
--- a/PM3-Bench/README.md
+++ b/PM3-Bench/README.md
@@ -0,0 +1,24 @@
+# PM3-Bench
+
+## Introduction
+The [ClinGen Evidence Repository](https://erepo.clinicalgenome.org/evrepo/)  provides expert-curated assertions, they are written in plain English, posing a difficult challenge for automated evaluation of benchmarks. To address this, we created PM3-Bench, a comprehensive dataset for PM3 literature evidence extraction, based on the ClinGen Evidence Repository
+
+![](../images/PM3-bench.png)
+
+---
+
+## Description
+We provide the `PM3-Bench.json` in this repo, which includes the following fields:
+| Column Name | Description | 
+|---| --- |
+| ClinGen ID | The original ID in the ClinGen Evidence Repository |
+| Variant Name | The HGVS name of the variant (DNA change) |
+| Condition | The condition reported in ClinGen |
+| Criterion | The met ACMG criteria |
+| Raw Comment |The expert-submitted comment |
+| PMID | The PubMed ID of the literature evidence  |
+| Number of Patients | Extracted number of patients based on the comments |
+| In trans Variants  | List of in trans variants extracted from the comments, augmented in all possible formats, separated by space. "NA" means no in trans variant was mentioned in the raw comments |
+| labels | `eval`: variant-publication pairs for evaluations; `others`: truncated publication XML file in NCBI API, removed in evaluation; `fine-tune`: remaining samples, where non-empty comments used for fine-tuning|
+
+
diff --git a/README.md b/README.md
index cb9140c..f183c9c 100644
--- a/README.md
+++ b/README.md
@@ -23,6 +23,7 @@ We introduce AutoPM3, a method for automating the extraction of ACMG/AMP PM3 evi
 - [Usage](#usage)
     - [Quick Start](#quick-start)
     - [Advanced Usage](#advanced-usage-of-the-python-script)
+- [PM3-Bench](#pm3-bench)
 - [TODO](#todo)
 ---
 
@@ -47,7 +48,6 @@ mkdir ollama_models
 export OLLAMA_MODELS=./ollama_models
 ```
 
-3. Launch Ollama server:
 
 ```bash
 
@@ -108,5 +108,8 @@ python AutoPM3_main.py
 --model_name_text llama3_loraFT-8b-f16 ## change to llama3:70b or other hosted models as the backend of RAG as you prefer, noted that you need pull the model in Ollama in advance.
 ```
 
+## PM3-Bench
+* We released PM3-Bench used in this study, details listed in [PM3-Bench tutorial](PM3-Bench/README.md)
+
 ## TODO
 * A fast set up for AutoPM3.
\ No newline at end of file
diff --git a/images/PM3-bench.png b/images/PM3-bench.png
new file mode 100644
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