NM_000258.3(MYL3):c.235G>A (p.Val79Ile) AND Cardiomyopathy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 26, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000777873.7

Allele description [Variation Report for NM_000258.3(MYL3):c.235G>A (p.Val79Ile)]

NM_000258.3(MYL3):c.235G>A (p.Val79Ile)

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.235G>A (p.Val79Ile)

HGVS:

NC_000003.12:g.46860748C>T
NG_007555.2:g.26422G>A
NM_000258.3:c.235G>AMANE SELECT
NP_000249.1:p.Val79Ile
NP_000249.1:p.Val79Ile
LRG_395t1:c.235G>A
LRG_395:g.26422G>A
LRG_395p1:p.Val79Ile
NC_000003.11:g.46902238C>T
NM_000258.2:c.235G>A

Protein change:

V79I

Links:

dbSNP: rs150634297

NCBI 1000 Genomes Browser:

rs150634297

Molecular consequence:

NM_000258.3:c.235G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000913880	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 26, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22957257, 25741868
SCV001333536	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 24, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000913880

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 26, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001333536

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 24, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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 Myosin essential light chain mutation causes hypertrophic cardiomyopathy with late onset and low expressivity.

Andersen PS, Hedley PL, Page SP, Syrris P, Moolman-Smook JC, McKenna WJ, Elliott PM, Christiansen M.

Biochem Res Int. 2012;2012:685108. doi: 10.1155/2012/685108. Epub 2012 Apr 11.

PubMed [citation]

PMID:: 22957257
PMCID:: PMC3432877

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000913880.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces valine with isoleucine at codon 79 of the MYL3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual with a mild form of late-onset hypertrophic cardiomyopathy (PMID: 22957257). However, three carriers from this family had ECG and/or echocardiographic abnormalities that did not fulfill diagnostic criteria for hypertrophic cardiomyopathy. In addition, five carriers from this family showed normal phenotype. This variant has been identified in 7/251470 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV001333536.1

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

#	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: Apr 20, 2024

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