NM_000258.3(MYL3):c.188G>A (p.Arg63His) AND Cardiomyopathy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 31, 2023
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:: RCV000770182.7

Allele description [Variation Report for NM_000258.3(MYL3):c.188G>A (p.Arg63His)]

NM_000258.3(MYL3):c.188G>A (p.Arg63His)

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.188G>A (p.Arg63His)

HGVS:

NC_000003.12:g.46860795C>T
NG_007555.2:g.26375G>A
NM_000258.3:c.188G>AMANE SELECT
NP_000249.1:p.Arg63His
NP_000249.1:p.Arg63His
LRG_395t1:c.188G>A
LRG_395:g.26375G>A
LRG_395p1:p.Arg63His
NC_000003.11:g.46902285C>T
NM_000258.2:c.188G>A

Protein change:

R63H

Links:

dbSNP: rs139354105

NCBI 1000 Genomes Browser:

rs139354105

Molecular consequence:

NM_000258.3:c.188G>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
SCV000901609	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 7, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000907415	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 31, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25351510, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000901609

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 7, 2015)

germline

clinical testing

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

SCV000907415

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 31, 2023)

germline

clinical testing

PubMed (2)
[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

Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.

Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM.

Heart. 2015 Feb;101(4):294-301. doi: 10.1136/heartjnl-2014-306387. Epub 2014 Oct 28.

PubMed [citation]

PMID:: 25351510
PMCID:: PMC4345808

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 CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository, SCV000901609.1

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000907415.4

#	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 arginine with histidine at codon 63 of the MYL3 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25351510). This variant has also been identified in 6/251466 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

Last Updated: Sep 29, 2024

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