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.2609G>A (p.Arg870His)

Curation History

CA012740

14120 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2d09f591-2d8e-40af-a273-07a3ec1e0fc5

Approved on: 2016-12-15

Published on: 2018-11-16

HGVS expressions

NM_000257.3:c.2609G>A

NM_000257.3(MYH7):c.2609G>A (p.Arg870His)

NC_000014.9:g.23424839C>T

CM000676.2:g.23424839C>T

NC_000014.8:g.23894048C>T

CM000676.1:g.23894048C>T

NC_000014.7:g.22963888C>T

NG_007884.1:g.15823G>A

NM_000257.4:c.2609G>A

ENST00000355349.3:c.2609G>A

Pathogenic

PM2 PM1 PS4 PP1_Strong

Evidence Links 4

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2609G>A (p.Arg870His) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy (PS4; PMID:7796500; PMID:12974739; PMID:17703256; PMID:27532257; Partners LMM ClinVar SCV000059458.5; SHaRe consortium, PMID: 30297972). This variant segregated with disease in >10 affected individuals (PP1_Strong; PMID:7796500; PMID:12974739; PMID:17703256). This variant was identified in 1/66732 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

PM2

Identified in 1/66732 European chromosomes

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

PS4

>20 probands with HCM including ClinVar SCV000059458.5 and SHaRe data

Variant identified in 13 probands with HCM PubMed:27532257

Variant found in 3 probands with HCM PubMed:7796500

Variant identified in 1 proband with HCM PubMed:17703256

Variant identified in 2 probands with HCM PubMed:12974739

PP1_Strong

>10 segregations

Variant segregated with disease in 6 affected family members PubMed:7796500

Variant segregated with disease in 7 affected family members PubMed:17703256

Variant segregated with disease in 3 affected individuals PubMed:12974739

Curation History

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