NM_000432.4(MYL2):c.433G>A (p.Asp145Asn) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 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:: RCV003323424.2

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]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004028700	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 10, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28611029, 35629155 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004028700

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jul 10, 2023)

germline

clinical testing

PubMed (2)
[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

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

Signal-to-Noise Analysis Can Inform the Likelihood That Incidentally Identified Variants in Sarcomeric Genes Are Associated with Pediatric Cardiomyopathy.

Kurzlechner LM, Jones EG, Berkman AM, Tadros HJ, Rosenfeld JA, Yang Y, Tunuguntla H, Allen HD, Kim JJ, Landstrom AP.

J Pers Med. 2022 Apr 30;12(5). doi:pii: 733. 10.3390/jpm12050733.

PubMed [citation]

PMID:: 35629155
PMCID:: PMC9145017

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004028700.1

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

Description

Variant summary: MYL2 c.433G>A (p.Asp145Asn) results in a conservative amino acid change located in the EF-hand domain (IPR002048) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 249004 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.433G>A has been reported in the literature in at least one individual affected with Hypertrophic Cardiomyopathy, reported as a VUS (example: Haskell_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Hypertrophic Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28611029, 35629155). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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: May 7, 2024

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