NM_000257.4(MYH7):c.115G>A (p.Val39Met) AND Hypertrophic cardiomyopathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 20, 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:: RCV000559649.6

Allele description

NM_000257.4(MYH7):c.115G>A (p.Val39Met)

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.115G>A (p.Val39Met)

HGVS:

NC_000014.9:g.23433618C>T
NG_007884.1:g.7044G>A
NM_000257.4:c.115G>AMANE SELECT
NP_000248.2:p.Val39Met
LRG_384t1:c.115G>A
LRG_384:g.7044G>A
NC_000014.8:g.23902827C>T
NM_000257.2:c.115G>A
NM_000257.3:c.115G>A
P12883:p.Val39Met
c.115G>A

Protein change:

V39M

Links:

UniProtKB: P12883#VAR_019845; dbSNP: rs376160714

NCBI 1000 Genomes Browser:

rs376160714

Molecular consequence:

NM_000257.4:c.115G>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

Recent activity

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serine/threonine-protein kinase PAK 5 isoform X2 [Gallus gallus]
serine/threonine-protein kinase PAK 5 isoform X2 [Gallus gallus]
gi|2201783625|ref|XP_046769387.1|

Protein
PREDICTED: Gallus gallus p21 (RAC1) activated kinase 5 (PAK5), transcript varian...
PREDICTED: Gallus gallus p21 (RAC1) activated kinase 5 (PAK5), transcript variant X5, mRNA
gi|2201665421|ref|XM_046938629.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000623635	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 20, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12707239, 27247418, 27532257, 28798025, 32833721, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000623635

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 20, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy.

Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M; EUROGENE Heart Failure Project..

Circulation. 2003 May 6;107(17):2227-32. Epub 2003 Apr 21. Erratum in: Circulation. 2004 Jun 29;109(25):3258.

PubMed [citation]

PMID:: 12707239

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation.

Homburger JR, Green EM, Caleshu C, Sunitha MS, Taylor RE, Ruppel KM, Metpally RP, Colan SD, Michels M, Day SM, Olivotto I, Bustamante CD, Dewey FE, Ho CY, Spudich JA, Ashley EA.

Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):6701-6. doi: 10.1073/pnas.1606950113. Epub 2016 May 31.

PubMed [citation]

PMID:: 27247418
PMCID:: PMC4914177

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000623635.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 39 of the MYH7 protein (p.Val39Met). This variant is present in population databases (rs376160714, gnomAD 0.05%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy, Laing distal myopathy, and/or left ventricular noncompaction (PMID: 12707239, 27247418, 27532257, 28798025, 32833721). ClinVar contains an entry for this variant (Variation ID: 42827). 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%. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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