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.1988G>A (p.Arg663His)

Curation History

CA011552

42875 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b27a29bf-ad68-4066-b07a-e5dcac3e6944

Approved on: 2016-12-15

Published on: 2018-11-16

HGVS expressions

NM_000257.3:c.1988G>A

NM_000257.3(MYH7):c.1988G>A (p.Arg663His)

NM_000257.4:c.1988G>A

ENST00000355349.3:c.1988G>A

NC_000014.9:g.23426833C>T

CM000676.2:g.23426833C>T

NC_000014.8:g.23896042C>T

CM000676.1:g.23896042C>T

NC_000014.7:g.22965882C>T

NG_007884.1:g.13829G>A

Pathogenic

PP1_Strong PS4 PM2 PM1

Evidence Links 7

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.1988G>A (p.Arg663His) variant in MYH7 has been reported in >30 individuals with hypertrophic cardiomyopathy (PS4; PMID:27532257; PMID:10750581; PMID:11133230; PMID:12707239; PMID:15563892; PMID:16199542; PMID:15358028; AGCMC Sydney ClinVar SCV000212629.1; Invitae ClinVar SCV000219103.7; Partners LMM ClinVar SCV000059409.5; SHaRe consortium, PMID: 30297972). This variant segregated with disease in >15 affected individuals (PP1_Strong; PMID:10750581; Partners LMM ClinVar SCV000059409.5; SHaRe consortium, PMID: 30297972). This variant was identified in 2/66718 European chromosomes (PM2; http://exac.broadinstitute.org). This variant lies in the head region of the protein (aa 181-937) and missense variants in this region are statistically more likely to be disease-associated (PM1; PMID:27532257). In summary, this variant meets criteria to be classified as pathogenic for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PS4; PP1_ Strong; PM1; PM2

PP1_Strong

>15 segregations (including SHaRe data, ClinVar SCV000059409.5)

Variant segregated with disease in 15 affected family members PubMed:10750581

PS4

>30 probands with HCM (including ClinVar SCV000212629.1; ClinVar SCV000219103.7; ClinVar SCV000059409.5; SHaRe data)

Variant identified in cases with HCM PubMed:27532257

Variant identified in 2 probands with HCM PubMed:16199542

Variant identified in 8 probands with HCM PubMed:15358028

Variant identified in 1 proband with HCM PubMed:11133230

Variant identified in 2 probands with HCM PubMed:10750581

Variant identified in 2 probands with HCM PubMed:12707239

Variant identified in 4 probands with HCM PubMed:15563892

PM2

Identified in 2/66718 Europeans chrs in ExAC

PM1

Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated

Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated PubMed:27532257

Curation History

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