NM_000257.4(MYH7):c.1012G>A (p.Val338Met) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 12, 2021
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:: RCV002345472.2

Allele description [Variation Report for NM_000257.4(MYH7):c.1012G>A (p.Val338Met)]

NM_000257.4(MYH7):c.1012G>A (p.Val338Met)

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.1012G>A (p.Val338Met)

Other names:

p.V338M:GTG>ATG; NM_000257.4(MYH7):c.1012G>A

HGVS:

NC_000014.9:g.23429901C>T
NG_007884.1:g.10761G>A
NM_000257.4:c.1012G>AMANE SELECT
NP_000248.2:p.Val338Met
LRG_384t1:c.1012G>A
LRG_384:g.10761G>A
NC_000014.8:g.23899110C>T
NM_000257.2:c.1012G>A
NM_000257.3:c.1012G>A

Protein change:

V338M

Links:

dbSNP: rs727503271

NCBI 1000 Genomes Browser:

rs727503271

Molecular consequence:

NM_000257.4:c.1012G>A - 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
SCV002620615	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jul 12, 2021)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 20474083, 23549607, 23690394, 25228707, 25611685, 27247418, 27532257, 28241245, 28606303, 28771489 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002620615

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jul 12, 2021)

germline

clinical testing

PubMed (10)
[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

A novel custom resequencing array for dilated cardiomyopathy.

Zimmerman RS, Cox S, Lakdawala NK, Cirino A, Mancini-DiNardo D, Clark E, Leon A, Duffy E, White E, Baxter S, Alaamery M, Farwell L, Weiss S, Seidman CE, Seidman JG, Ho CY, Rehm HL, Funke BH.

Genet Med. 2010 May;12(5):268-78. doi: 10.1097/GIM.0b013e3181d6f7c0.

PubMed [citation]

PMID:: 20474083
PMCID:: PMC3018746

T1 measurements identify extracellular volume expansion in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy.

Ho CY, Abbasi SA, Neilan TG, Shah RV, Chen Y, Heydari B, Cirino AL, Lakdawala NK, Orav EJ, González A, López B, Díez J, Jerosch-Herold M, Kwong RY.

Circ Cardiovasc Imaging. 2013 May 1;6(3):415-22. doi: 10.1161/CIRCIMAGING.112.000333. Epub 2013 Apr 2.

PubMed [citation]

PMID:: 23549607
PMCID:: PMC3769196

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV002620615.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

The p.V338M variant (also known as c.1012G>A), located in coding exon 10 of the MYH7 gene, results from a G to A substitution at nucleotide position 1012. The valine at codon 338 is replaced by methionine, an amino acid with highly similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). This alteration has been detected in several individuals from hypertrophic cardiomyopathy (HCM) cohorts and cohorts referred for HCM genetic testing, and has shown some segregation with disease (Ho CY et al. Circ Cardiovasc Imaging, 2013 May;6:415-22; Captur G et al. Circ Cardiovasc Imaging. 2014;7:863-71; Homburger JR et al. Proc Natl Acad Sci USA. 2016;113(24):6701-6; Walsh R et al. Genet Med. 2017;19(2):192-203; Chida A et al. Heart Vessels. 2017 Jun;32(6):700-707; Mademont-Soler I et al. PLoS One. 2017 Aug;12(8):e0181465). In addition, this alteration has been detected by an outside laboratory in two probands reported to have HCM, and was reported to segregate with disease in multiple affected individuals from one family (LMM pers. comm.). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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: May 1, 2024

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