NM_000257.4(MYH7):c.789A>G (p.Ile263Met) AND Hypertrophic cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Jun 20, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001210689.2

Allele description [Variation Report for NM_000257.4(MYH7):c.789A>G (p.Ile263Met)]

NM_000257.4(MYH7):c.789A>G (p.Ile263Met)

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.789A>G (p.Ile263Met)
HGVS:
  • NC_000014.9:g.23431425T>C
  • NG_007884.1:g.9237A>G
  • NM_000257.4:c.789A>GMANE SELECT
  • NP_000248.2:p.Ile263Met
  • LRG_384t1:c.789A>G
  • LRG_384:g.9237A>G
  • NC_000014.8:g.23900634T>C
  • NM_000257.2:c.789A>G
  • NM_000257.3:c.789A>G
  • P12883:p.Ile263Met
Protein change:
I263M
Links:
UniProtKB: P12883#VAR_042772; dbSNP: rs730880855
NCBI 1000 Genomes Browser:
rs730880855
Molecular consequence:
  • NM_000257.4:c.789A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypertrophic cardiomyopathy
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001382187Invitaecriteria provided, single submitter
Uncertain significance
(Jun 20, 2019)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy.

Van Driest SL, Jaeger MA, Ommen SR, Will ML, Gersh BJ, Tajik AJ, Ackerman MJ.

J Am Coll Cardiol. 2004 Aug 4;44(3):602-10.

PubMed [citation]
PMID:
15358028

Genotype-phenotype analysis in four families with mutations in beta-myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy.

Tesson F, Richard P, Charron P, Mathieu B, Cruaud C, Carrier L, Dubourg O, Lautié N, Desnos M, Millaire A, Isnard R, Hagege AA, Bouhour JB, Bennaceur M, Hainque B, Guicheney P, Schwartz K, Komajda M.

Hum Mutat. 1998;12(6):385-92.

PubMed [citation]
PMID:
9829907
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV001382187.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces isoleucine with methionine at codon 263 of the MYH7 protein (p.Ile263Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in in individuals affected with hypertrophic cardiomyopathy (PMID: 15358028, 27532257). ClinVar contains an entry for this variant (Variation ID: 181326). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). This variant disrupts the p.Ile263 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9829907, 24093860, 27247418, 27532257, 21425739, 12707239, 15008060). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

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