NM_000257.4(MYH7):c.1750G>A (p.Gly584Ser) AND Primary familial hypertrophic cardiomyopathy

Clinical significance:Pathogenic (Last evaluated: Oct 1, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000035743.6

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]

Condition(s)

Name:
Primary familial hypertrophic cardiomyopathy (HCM)
Synonyms:
Hereditary ventricular hypertrophy; Idiopathic hypertrophic subaortic stenosis
Identifiers:
MONDO: MONDO:0024573; MeSH: D024741; MedGen: C0949658; OMIM: PS192600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000917844Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Oct 1, 2018)
germlineclinical testing

PubMed (7)
[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

Characterization of a phenotype-based genetic test prediction score for unrelated patients with hypertrophic cardiomyopathy.

Bos JM, Will ML, Gersh BJ, Kruisselbrink TM, Ommen SR, Ackerman MJ.

Mayo Clin Proc. 2014 Jun;89(6):727-37. doi: 10.1016/j.mayocp.2014.01.025. Epub 2014 May 1.

PubMed [citation]
PMID:
24793961
PMCID:
PMC4234122

Array-based resequencing assay for mutations causing hypertrophic cardiomyopathy.

Waldmüller S, Müller M, Rackebrandt K, Binner P, Poths S, Bonin M, Scheffold T.

Clin Chem. 2008 Apr;54(4):682-7. doi: 10.1373/clinchem.2007.099119. Epub 2008 Feb 7.

PubMed [citation]
PMID:
18258667
PMCID:
PMC7108484
See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917844.1

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

Description

Variant summary: MYH7 c.1750G>A (p.Gly584Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 247226 control chromosomes. c.1750G>A has been reported in the literature in multiple individuals affected with Hypertrophic Cardiomyopathy. A variant at the same codon, p.Gly584Arg, as well as variants in adjacent codons, have been associated with HCM, suggesting the codon and motif are critical for function. Together, these data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 27, 2021

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