NM_000432.4(MYL2):c.433G>A (p.Asp145Asn) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 1, 2023
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:: RCV003995672.2

Allele description [Variation Report for NM_000432.4(MYL2):c.433G>A (p.Asp145Asn)]

NM_000432.4(MYL2):c.433G>A (p.Asp145Asn)

Gene:

MYL2:myosin light chain 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.11

Genomic location:

Preferred name:

NM_000432.4(MYL2):c.433G>A (p.Asp145Asn)

HGVS:

NC_000012.12:g.110911145C>T
NG_007554.1:g.14433G>A
NM_000432.4:c.433G>AMANE SELECT
NP_000423.2:p.Asp145Asn
NP_000423.2:p.Asp145Asn
LRG_393t1:c.433G>A
LRG_393:g.14433G>A
LRG_393p1:p.Asp145Asn
NC_000012.11:g.111348949C>T
NM_000432.3:c.433G>A

Protein change:

D145N

Links:

dbSNP: rs199567559

NCBI 1000 Genomes Browser:

rs199567559

Molecular consequence:

NM_000432.4:c.433G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004845818	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Dec 1, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28611029, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004845818

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Dec 1, 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	11	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Whole Exome Sequencing Identifies Truncating Variants in Nuclear Envelope Genes in Patients With Cardiovascular Disease.

Haskell GT, Jensen BC, Samsa LA, Marchuk D, Huang W, Skrzynia C, Tilley C, Seifert BA, Rivera-Muñoz EA, Koller B, Wilhelmsen KC, Liu J, Alhosaini H, Weck KE, Evans JP, Berg JS.

Circ Cardiovasc Genet. 2017 Jun;10(3). doi:pii: e001443. 10.1161/CIRCGENETICS.116.001443.

PubMed [citation]

PMID:: 28611029
PMCID:: PMC5497793

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 All of Us Research Program, National Institutes of Health, SCV004845818.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	11	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces aspartic acid with asparagine at codon 145 of the MYL2 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: 28611029). This variant has been identified in 5/249004 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	108544	not provided	not provided		11	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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