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NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 21, 2024
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:
RCV000617211.6

Allele description [Variation Report for NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp)]

NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp)

Genes:
MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
MHRT:myosin heavy chain associated RNA transcript [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q11.2
Genomic location:
Preferred name:
NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp)
HGVS:
  • NC_000014.9:g.23417174G>A
  • NG_007884.1:g.23488C>T
  • NM_000257.4:c.4498C>TMANE SELECT
  • NP_000248.2:p.Arg1500Trp
  • LRG_384t1:c.4498C>T
  • LRG_384:g.23488C>T
  • NC_000014.8:g.23886383G>A
  • NM_000257.2:c.4498C>T
  • NM_000257.3:c.4498C>T
Protein change:
R1500W
Links:
dbSNP: rs45544633
NCBI 1000 Genomes Browser:
rs45544633
Molecular consequence:
  • NM_000257.4:c.4498C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000737223Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Likely pathogenic
(May 21, 2024)
germlineclinical testing

PubMed (15)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Two novel mutations in the beta-myosin heavy chain gene associated with dilated cardiomyopathy.

Kärkkäinen S, Heliö T, Jääskeläinen P, Miettinen R, Tuomainen P, Ylitalo K, Kaartinen M, Reissell E, Toivonen L, Nieminen MS, Kuusisto J, Laakso M, Peuhkurinen K.

Eur J Heart Fail. 2004 Dec;6(7):861-8.

PubMed [citation]
PMID:
15556047

Cardiac magnetic resonance imaging of myocardial contrast uptake and blood flow in patients affected with idiopathic or familial dilated cardiomyopathy.

Jerosch-Herold M, Sheridan DC, Kushner JD, Nauman D, Burgess D, Dutton D, Alharethi R, Li D, Hershberger RE.

Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1234-H1242. doi: 10.1152/ajpheart.00429.2008. Epub 2008 Jul 25.

PubMed [citation]
PMID:
18660445
PMCID:
PMC2544489
See all PubMed Citations (15)

Details of each submission

From Ambry Genetics, SCV000737223.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (15)

Description

The p.R1500W variant (also known as c.4498C>T), located in coding exon 30 of the MYH7 gene, results from a C to T substitution at nucleotide position 4498. The arginine at codon 1500 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in several dilated cardiomyopathy (DCM) cohorts (Kärkkäinen S et al. Eur. J. Heart Fail. 2004;6:861-8; Hershberger RE et al. Clin Transl Sci. 2008;1:21-6; Jerosch-Herold M et al. Am. J. Physiol. Heart Circ. Physiol. 2008;295:H1234-H1242; Merlo M et al. Clin Transl Sci. 2013;6:424-8; Forleo C et al. PLoS ONE. 2017;12:e0181842). In vitro studies suggest that this alteration has an impact on filament formation; however, the same effect was not reproduced in vivo (Armel TZ et al. J. Mol. Cell. Cardiol., 2010 May;48:1007-13; Buvoli M et al. J. Mol. Biol. 2012;415:807-18; Wolny M et al. J. Biol. Chem., 2013 Nov;288:31952-62). 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 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: Nov 10, 2024