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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000257.3(MYH7):c.1207C>T (p.Arg403Trp)

CA010360

14102 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d065fb29-95bd-49a8-951e-f52b10fac57c

HGVS expressions

NM_000257.3:c.1207C>T

NM_000257.3(MYH7):c.1207C>T (p.Arg403Trp)

NC_000014.9:g.23429279G>A

CM000676.2:g.23429279G>A

NC_000014.8:g.23898488G>A

CM000676.1:g.23898488G>A

NC_000014.7:g.22968328G>A

NG_007884.1:g.11383C>T

NM_000257.4:c.1207C>T

ENST00000355349.3:c.1207C>T

Pathogenic

PS4 PP3 PP1_Strong PM2 PM5 PM1

Evidence Links 4

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.1207C>T (p.Arg403Trp) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy and segregated with disease in >20 affected family members (PS4 and PP1_Strong; PMID:1052196; PMID:7662452; PMID:7848420; PMID:8254035; PMID:8268932; PMID:12707239; PMID:12974739; PMID:15010274; PMID:15856146; PMID:17612745; PMID:20428263; PMID:21239446; PMID:26383716; Partners LMM ClinVar SCV000059358.5; AGCMC Sydney ClinVar SCV000212643.1; SHaRe consortium, PMID: 30297972). 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.1208G>A p.Arg403Gln - Variation ID 14087). 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

PS4

>20 probands with HCM reported

PP3

Tools suggest damaging

PP1_Strong

>20 segregations

Variant segregated with disease in 12 family members PubMed:7662452

Variant segregated with disease in 11 family members PubMed:17612745

Variant segregated with disease in 5 affected family members PubMed:8254035

PM2

Absent from ExAC

PM5

c.1208G>A (p.Arg403Gln) - Variation ID 14087 - Pathogenic by ClinGen 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.