Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000257.3(MYH7):c.5326A>G (p.Ser1776Gly)

Curation History

CA015944

177629 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5d9a840f-4e17-4378-a41d-341cf6eab7b8

Approved on: 2016-12-15

Published on: 2018-11-16

HGVS expressions

NM_000257.3:c.5326A>G

NM_000257.3(MYH7):c.5326A>G (p.Ser1776Gly)

NM_000257.4:c.5326A>G

ENST00000355349.3:c.5326A>G

NC_000014.9:g.23415228T>C

CM000676.2:g.23415228T>C

NC_000014.8:g.23884437T>C

CM000676.1:g.23884437T>C

NC_000014.7:g.22954277T>C

NG_007884.1:g.25434A>G

Uncertain Significance

PP3

PM2 PS4

Evidence Links 3

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.5326A>G (p.Ser1776Gly) variant in MYH7 has been reported in 12 individuals with hypertrophic cardiomyopathy (PMID:27532257; PMID:11861413; PMID:21239446; Partners LMM ClinVar SCV000203861.4; SHaRe consortium, PMID: 30297972) but has also been identified in 0.02% (2/8654) of East Asian chromosomes by ExAC (http://exac.broadinstitute.org). Since the MYH7 specifications state that PS4 is only applicable if the variant is absent or rare in large population studies, PS4 criterion was not applied (PMID:29300372). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). In summary, this variant meets criteria to be classified as uncertain significance for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PP3

PP3

Tools predict damaging

PM2

Variant identified in 2/8654 East Asian chr in ExAC

PS4

Variant identified in 12 probands with HCM, but PS4 criterion not applied since PM2 was not met

Variant identified in 1 proband with HCM PubMed:11861413

Variant identified in probands with HCM PubMed:27532257

Variant identified in 1 proband with HCM PubMed:21239446

Curation History

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