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NM_000257.4(MYH7):c.1207C>T (p.Arg403Trp) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 19, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000621657.4

Allele description [Variation Report for NM_000257.4(MYH7):c.1207C>T (p.Arg403Trp)]

NM_000257.4(MYH7):c.1207C>T (p.Arg403Trp)

Gene:
MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q11.2
Genomic location:
Preferred name:
NM_000257.4(MYH7):c.1207C>T (p.Arg403Trp)
Other names:
p.R403W:CGG>TGG; NM_000257.3(MYH7):c.1207C>T
HGVS:
  • NC_000014.9:g.23429279G>A
  • NG_007884.1:g.11383C>T
  • NM_000257.4:c.1207C>TMANE SELECT
  • NP_000248.2:p.Arg403Trp
  • LRG_384t1:c.1207C>T
  • LRG_384:g.11383C>T
  • NC_000014.8:g.23898488G>A
  • NM_000257.2:c.1207C>T
  • NM_000257.3:c.1207C>T
  • P12883:p.Arg403Trp
  • c.1207C>T
Protein change:
R403W; ARG403TRP
Links:
UniProtKB: P12883#VAR_004575; OMIM: 160760.0015; dbSNP: rs3218714
NCBI 1000 Genomes Browser:
rs3218714
Molecular consequence:
  • NM_000257.4:c.1207C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000740195Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Apr 19, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Functional consequences of mutations in the smooth muscle myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy.

Yamashita H, Tyska MJ, Warshaw DM, Lowey S, Trybus KM.

J Biol Chem. 2000 Sep 8;275(36):28045-52.

PubMed [citation]
PMID:
10882745

Human homozygous R403W mutant cardiac myosin presents disproportionate enhancement of mechanical and enzymatic properties.

Keller DI, Coirault C, Rau T, Cheav T, Weyand M, Amann K, Lecarpentier Y, Richard P, Eschenhagen T, Carrier L.

J Mol Cell Cardiol. 2004 Mar;36(3):355-62.

PubMed [citation]
PMID:
15010274
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000740195.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The p.R403W pathogenic mutation (also known as c.1207C>T), located in coding exon 11 of the MYH7 gene, results from a C to T substitution at nucleotide position 1207. The arginine at codon 403 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in individuals and families with hypertrophic cardiomyopathy (HCM), with co-segregation in multiple families demonstrating variable penetrance and expressivity (Dausse E et al. J. Clin. Invest., 1993 Dec;92:2807-13; Posen BM et al. Br Heart J, 1995 Jul;74:40-6; Walsh R et al. Genet. Med., 2017 Feb;19:192-203). Functional studies have exhibited increased actin sliding velocity and enzymatic activity (Yamashita H et al. J. Biol. Chem., 2000 Sep;275:28045-52; Keller DI et al. J. Mol. Cell. Cardiol., 2004 Mar;36:355-62). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 17, 2024