NM_000257.4(MYH7):c.1319T>C (p.Val440Ala) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 26, 2020
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:: RCV002384363.2

Allele description [Variation Report for NM_000257.4(MYH7):c.1319T>C (p.Val440Ala)]

NM_000257.4(MYH7):c.1319T>C (p.Val440Ala)

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.1319T>C (p.Val440Ala)

HGVS:

NC_000014.9:g.23429043A>G
NG_007884.1:g.11619T>C
NM_000257.4:c.1319T>CMANE SELECT
NP_000248.2:p.Val440Ala
LRG_384:g.11619T>C
NC_000014.8:g.23898252A>G
NM_000257.2:c.1319T>C

Protein change:

V440A

Links:

dbSNP: rs1244840759

NCBI 1000 Genomes Browser:

rs1244840759

Molecular consequence:

NM_000257.4:c.1319T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002689734	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Aug 26, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15358028, 24793961, 27532257, 30275503, 30847666 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002689734

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Aug 26, 2020)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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

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

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

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002689734.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.V440A variant (also known as c.1319T>C), located in coding exon 12 of the MYH7 gene, results from a T to C substitution at nucleotide position 1319. The valine at codon 440 is replaced by alanine, an amino acid with similar properties. This alteration is located in the head domain of the MYH7 protein, which has limited benign variation, and has been detected in hypertrophic cardiomyopathy (HCM) cohorts; however, details were limited (Bos JM et al. Mayo Clin. Proc., 2014 Jun;89:727-37; van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This allele was reported in only one heterozygous individual in population-based cohorts in the Genome Aggregation Database (gnomAD). A different variant affecting this codon (p.V440M, c.1318G>A) has also been detected in HCM cohorts, with several clinical labs reporting segregation with disease (Van Driest SL et al. J. Am. Coll. Cardiol., 2004 Aug;44:602-10; Bos JM et al. Mayo Clin. Proc., 2014 Jun;89:727-37; Walsh R et al. Genet. Med., 2017 02;19:192-203; LMM pers comm; OMGL pers comm). 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.

#	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: Sep 29, 2024

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