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NM_000257.4(MYH7):c.746G>A (p.Arg249Gln) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 21, 2021
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:
RCV000617265.4

Allele description [Variation Report for NM_000257.4(MYH7):c.746G>A (p.Arg249Gln)]

NM_000257.4(MYH7):c.746G>A (p.Arg249Gln)

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.746G>A (p.Arg249Gln)
Other names:
p.R249Q:CGA>CAA
HGVS:
  • NC_000014.9:g.23431468C>T
  • NG_007884.1:g.9194G>A
  • NM_000257.4:c.746G>AMANE SELECT
  • NP_000248.2:p.Arg249Gln
  • LRG_384t1:c.746G>A
  • LRG_384:g.9194G>A
  • NC_000014.8:g.23900677C>T
  • NM_000257.2:c.746G>A
  • NM_000257.3:c.746G>A
  • P12883:p.Arg249Gln
  • c.746G>A
Protein change:
R249Q; ARG249GLN
Links:
UniProtKB: P12883#VAR_004569; OMIM: 160760.0002; dbSNP: rs3218713
NCBI 1000 Genomes Browser:
rs3218713
Molecular consequence:
  • NM_000257.4:c.746G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000735517Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 21, 2021) 		germlineclinical testing

PubMed (27)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Coexistence of mitochondrial DNA and beta myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure.

Arbustini E, Fasani R, Morbini P, Diegoli M, Grasso M, Dal Bello B, Marangoni E, Banfi P, Banchieri N, Bellini O, Comi G, Narula J, Campana C, Gavazzi A, Danesino C, Viganò M.

Heart. 1998 Dec;80(6):548-58. Erratum in: Heart 1999 Mar;81(3):330.

PubMed [citation]
PMID:
10065021
PMCID:
PMC1728869

Beta-myosin heavy chain gene mutations and hypertrophic cardiomyopathy in Austrian children.

Greber-Platzer S, Marx M, Fleischmann C, Suppan C, Dobner M, Wimmer M.

J Mol Cell Cardiol. 2001 Jan;33(1):141-8.

PubMed [citation]
PMID:
11133230
See all PubMed Citations (27)

Details of each submission

From Ambry Genetics, SCV000735517.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (27)

Description

The p.R249Q pathogenic mutation (also known as c.746G>A), located in coding exon 7 of the MYH7 gene, results from a G to A substitution at nucleotide position 746. The arginine at codon 249 is replaced by glutamine, an amino acid with highly similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). This mutation has been reported in numerous individuals with hypertrophic cardiomyopathy (HCM), including two de novo cases, and has segregated with disease in multiple families (e.g., Rosenzweig A et al. N. Engl. J. Med. 1991;325:1753-60; Posen BM et al. Br Heart J. 1995;74:40-6; Arbustini E et al. Heart. 1998;80:548-58; Greber-Platzer S et al. J. Mol. Cell. Cardiol., 2001;33:141-8; Otsuka H et al. Circ. J. 2012;76:453-61; Kassem HSh et al. J Cardiovasc Transl Res. 2013;6:65-80; Marsiglia JD et al. Am. Heart J. 2013;166:775-82). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by BayesDel 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: Nov 3, 2024