NM_000258.3(MYL3):c.466G>A (p.Val156Met) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 10, 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:: RCV000617202.5

Allele description [Variation Report for NM_000258.3(MYL3):c.466G>A (p.Val156Met)]

NM_000258.3(MYL3):c.466G>A (p.Val156Met)

Gene:

MYL3:myosin light chain 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000258.3(MYL3):c.466G>A (p.Val156Met)

Other names:

p.V156M:GTG>ATG

HGVS:

NC_000003.12:g.46859490C>T
NG_007555.2:g.27680G>A
NM_000258.3:c.466G>AMANE SELECT
NP_000249.1:p.Val156Met
NP_000249.1:p.Val156Met
LRG_395t1:c.466G>A
LRG_395:g.27680G>A
LRG_395p1:p.Val156Met
NC_000003.11:g.46900980C>T
NM_000258.2:c.466G>A
c.466G>A
p.(Val156Met)

Protein change:

V156M

Links:

Leiden Muscular Dystrophy (MYL3): MYL3_00006; dbSNP: rs199474707

NCBI 1000 Genomes Browser:

rs199474707

Molecular consequence:

NM_000258.3:c.466G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

functional variant [Sequence Ontology: SO:0001536]

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
SCV000739969	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jun 10, 2024)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 16754800, 22958901, 23549607, 24111713, 25637381, 27532257, 30665703, 33495597, 35653365, 37466024 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000739969

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jun 10, 2024)

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

Single-gene mutations and increased left ventricular wall thickness in the community: the Framingham Heart Study.

Morita H, Larson MG, Barr SC, Vasan RS, O'Donnell CJ, Hirschhorn JN, Levy D, Corey D, Seidman CE, Seidman JG, Benjamin EJ.

Circulation. 2006 Jun 13;113(23):2697-705. Epub 2006 Jun 5.

PubMed [citation]

PMID:: 16754800

Burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study cohorts.

Bick AG, Flannick J, Ito K, Cheng S, Vasan RS, Parfenov MG, Herman DS, DePalma SR, Gupta N, Gabriel SB, Funke BH, Rehm HL, Benjamin EJ, Aragam J, Taylor HA Jr, Fox ER, Newton-Cheh C, Kathiresan S, O'Donnell CJ, Wilson JG, Altshuler DM, Hirschhorn JN, et al.

Am J Hum Genet. 2012 Sep 7;91(3):513-9. doi: 10.1016/j.ajhg.2012.07.017.

PubMed [citation]

PMID:: 22958901
PMCID:: PMC3511985

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV000739969.7

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

Description

The p.V156M variant (also known as c.466G>A), located in coding exon 4 of the MYL3 gene, results from a G to A substitution at nucleotide position 466. The valine at codon 156 is replaced by methionine, an amino acid with highly similar properties. This alteration has been reported in individuals with hypertrophic cardiomyopathy (HCM) (Berge KE et al. Clin Genet, 2014 Oct;86:355-60; Walsh R et al. Genet Med, 2017 Feb;19:192-203; Oktay V et al. Anatol J Cardiol. 2023 Nov 1;27(11):628-638; external communication; Ambry internal data). 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: Oct 26, 2024

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