NM_000257.4(MYH7):c.1750G>A (p.Gly584Ser) AND Cardiovascular phenotype

Clinical significance:Likely pathogenic (Last evaluated: Nov 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000242011.2

Allele description [Variation Report for NM_000257.4(MYH7):c.1750G>A (p.Gly584Ser)]

NM_000257.4(MYH7):c.1750G>A (p.Gly584Ser)

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.1750G>A (p.Gly584Ser)
HGVS:
  • NC_000014.9:g.23427723C>T
  • NG_007884.1:g.12939G>A
  • NM_000257.4:c.1750G>AMANE SELECT
  • NP_000248.2:p.Gly584Ser
  • LRG_384t1:c.1750G>A
  • LRG_384:g.12939G>A
  • NC_000014.8:g.23896932C>T
  • NM_000257.2:c.1750G>A
  • NM_000257.3:c.1750G>A
  • P12883:p.Gly584Ser
  • c.1750G>A
Protein change:
G584S
Links:
UniProtKB: P12883#VAR_029436; dbSNP: rs121913626
NCBI 1000 Genomes Browser:
rs121913626
Molecular consequence:
  • NM_000257.4:c.1750G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000319779Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Nov 12, 2019)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy.

Erdmann J, Daehmlow S, Wischke S, Senyuva M, Werner U, Raible J, Tanis N, Dyachenko S, Hummel M, Hetzer R, Regitz-Zagrosek V.

Clin Genet. 2003 Oct;64(4):339-49.

PubMed [citation]
PMID:
12974739

Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy.

Zou Y, Wang J, Liu X, Wang Y, Chen Y, Sun K, Gao S, Zhang C, Wang Z, Zhang Y, Feng X, Song Y, Wu Y, Zhang H, Jia L, Wang H, Wang D, Yan C, Lu M, Zhou X, Song L, Hui R.

Mol Biol Rep. 2013 Jun;40(6):3969-76. doi: 10.1007/s11033-012-2474-2. Epub 2013 Jan 3.

PubMed [citation]
PMID:
23283745
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000319779.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (7)

Description

The p.G584S variant (also known as c.1750G>A), located in coding exon 14 of the MYH7 gene, results from a G to A substitution at nucleotide position 1750. The glycine at codon 584 is replaced by serine, an amino acid with similar properties, and is located in the head domain. This alteration has been reported in multiple patients with hypertrophic cardiomyopathy (HCM) (Erdmann J et al. Clin Genet. 2003;64(4):339-49; Zou Y et al. Mol Biol Rep. 2013;40(6):3969-76; Kapplinger JD et al. J Cardiovasc Transl Res. 2014;7(3):347-61; Murphy SL et al. J Cardiovasc Transl Res. 2016;9:153-61; Haskell GT et al. Circ Cardiovasc Genet. 2017;10:e001443). Another alteration at the same codon, p.G584R (c.1750G>C), has also been associated with HCM (Watkins H et al. N Engl J Med. 1992;326(17):1108-14). 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
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Nov 27, 2021

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