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NM_000257.4(MYH7):c.746G>T (p.Arg249Leu) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 1, 2019
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:
RCV002388413.2

Allele description [Variation Report for NM_000257.4(MYH7):c.746G>T (p.Arg249Leu)]

NM_000257.4(MYH7):c.746G>T (p.Arg249Leu)

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>T (p.Arg249Leu)
HGVS:
  • NC_000014.9:g.23431468C>A
  • NG_007884.1:g.9194G>T
  • NM_000257.4:c.746G>TMANE SELECT
  • NP_000248.2:p.Arg249Leu
  • LRG_384t1:c.746G>T
  • LRG_384:g.9194G>T
  • NC_000014.8:g.23900677C>A
  • NM_000257.2:c.746G>T
Protein change:
R249L
Links:
dbSNP: rs3218713
NCBI 1000 Genomes Browser:
rs3218713
Molecular consequence:
  • NM_000257.4:c.746G>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
SCV002671733Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Mar 1, 2019) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

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

Citations

PubMed

A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction.

Tian T, Wang J, Wang H, Sun K, Wang Y, Jia L, Zou Y, Hui R, Zhou X, Song L.

Heart Vessels. 2015 Mar;30(2):258-64. doi: 10.1007/s00380-014-0503-x. Epub 2014 Apr 2.

PubMed [citation]
PMID:
24691700

Details of each submission

From Ambry Genetics, SCV002671733.2

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

Description

The p.R249L variant (also known as c.746G>T), located in coding exon 7 of the MYH7 gene, results from a G to T substitution at nucleotide position 746. The arginine at codon 249 is replaced by leucine, an amino acid with dissimilar properties. Other alterations affecting the same amino acid, p.R249Q (c.746G>A) and p.R249G (c.745C>G), have been reported in association with hypertrophic cardiomyopathy (HCM) and left ventricular non-compaction (LVNC) (Rosenzweig A et al. N. Engl. J. Med. 1991;325:1753-60; Tian T et al. Heart Vessels. 2015;30:258-64). In addition, this variant has been determined to be the result of a de novo mutation or germline mosaicism in one family with an isolated case of restrictive cardiomyopathy (Ambry internal data).This variant was not reported in population-based 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 majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: May 1, 2024