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]

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Variant: NM_000257.3(MYH7):c.2167C>G (p.Arg723Gly)

CA011843

42885 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6c2b587c-45cc-4fbc-bc0b-059a87ea6349

HGVS expressions

NM_000257.3:c.2167C>G

NM_000257.3(MYH7):c.2167C>G (p.Arg723Gly)

NC_000014.9:g.23425814G>C

CM000676.2:g.23425814G>C

NC_000014.8:g.23895023G>C

CM000676.1:g.23895023G>C

NC_000014.7:g.22964863G>C

NG_007884.1:g.14848C>G

NM_000257.4:c.2167C>G

ENST00000355349.3:c.2167C>G

Pathogenic

PP1_Strong PS4 PP3 PM2 PM5 PM1

Evidence Links 5

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2167C>G (p.Arg723Gly) variant in MYH7 has been reported in 12 individuals with hypertrophic cardiomyopathy (PS4; PMID:11113006; PMID:19150014; PMID:17097032; Partners LMM ClinVar SCV000059422.5; SHaRe consortium, PMID: 30297972). This variant segregated with disease in >20 affected individuals (PP1_Strong; PMID:11113006). This variant was absent from large population studies (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). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). A different pathogenic missense variant has been previously identified at this codon which may indicate that this residue is critical to the function of the protein (PM5; c.2167C>T p.Arg723Cys - ClinVar Variation ID 14095). 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; PM5; PP3

PP1_Strong

21 segregations

Variant segregated with disease in 21 affected family members PubMed:16630450

PS4

12 proband with HCM including ClinVar SCV000059422.5 and SHaRe data

Variant identified in 1 proband with HCM PubMed:19150014

Variant identified in 1 proband with HCM PubMed:27532257

Variant identified in 1 proband with HCM PubMed:17097032

Variant identified in 3 probands with HCM PubMed:11113006

PP3

Tool suggest damaging

PM2

Absent from ExAC

PM5

c.2167C>T (p.Arg723Cys) Pathogenic (Variation ID 14095) by Expert Panel

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

Approved on: 2016-12-15

Published on: 2018-11-16

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