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NM_000257.4(MYH7):c.3134G>A (p.Arg1045His) AND Hypertrophic cardiomyopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 20, 2023
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:
RCV000806326.5

Allele description [Variation Report for NM_000257.4(MYH7):c.3134G>A (p.Arg1045His)]

NM_000257.4(MYH7):c.3134G>A (p.Arg1045His)

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.3134G>A (p.Arg1045His)
HGVS:
  • NC_000014.9:g.23422291C>T
  • NG_007884.1:g.18371G>A
  • NM_000257.4:c.3134G>AMANE SELECT
  • NP_000248.2:p.Arg1045His
  • LRG_384:g.18371G>A
  • NC_000014.8:g.23891500C>T
  • NM_000257.2:c.3134G>A
  • NM_000257.3:c.3134G>A
Protein change:
R1045H
Links:
dbSNP: rs397516178
NCBI 1000 Genomes Browser:
rs397516178
Molecular consequence:
  • NM_000257.4:c.3134G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypertrophic cardiomyopathy
Synonyms:
HYPERTROPHIC MYOCARDIOPATHY
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
SCV000946317Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 20, 2023)
germlineclinical testing

PubMed (11)
[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

A child cohort study from southern Italy enlarges the genetic spectrum of hypertrophic cardiomyopathy.

Frisso G, Limongelli G, Pacileo G, Del Giudice A, Forgione L, CalabrĂ² P, Iacomino M, Detta N, Di Fonzo LM, Maddaloni V, CalabrĂ² R, Salvatore F.

Clin Genet. 2009 Jul;76(1):91-101. doi: 10.1111/j.1399-0004.2009.01190.x.

PubMed [citation]
PMID:
19659763

Genetics of hypertrophic cardiomyopathy in Norway.

Berge KE, Leren TP.

Clin Genet. 2014 Oct;86(4):355-60. doi: 10.1111/cge.12286. Epub 2013 Oct 23.

PubMed [citation]
PMID:
24111713
See all PubMed Citations (11)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000946317.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1045 of the MYH7 protein (p.Arg1045His). This variant is present in population databases (rs397516178, gnomAD 0.02%). This missense change has been observed in individuals with hypertrophic cardiomyopathy, dilated cardiomyopathy, or arrhythmogenic cardiomyopathy (PMID: 19659763, 24111713, 26199943, 26914223, 27247418, 30385303, 30462978). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 651054). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg1045 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18533079, 27247418, 27483260, 27532257). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024