NM_000432.4(MYL2):c.496G>C (p.Asp166His) AND Hypertrophic cardiomyopathy 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 23, 2021
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:: RCV002045135.5

Allele description [Variation Report for NM_000432.4(MYL2):c.496G>C (p.Asp166His)]

NM_000432.4(MYL2):c.496G>C (p.Asp166His)

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.496G>C (p.Asp166His)

HGVS:

NC_000012.12:g.110911082C>G
NG_007554.1:g.14496G>C
NM_000432.4:c.496G>CMANE SELECT
NP_000423.2:p.Asp166His
LRG_393:g.14496G>C
NC_000012.11:g.111348886C>G

Protein change:

D166H

Links:

dbSNP: rs730880952

NCBI 1000 Genomes Browser:

rs730880952

Molecular consequence:

NM_000432.4:c.496G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy 10
Synonyms:: CARDIOMYOPATHY, HYPERTROPHIC, MID-LEFT VENTRICULAR CHAMBER TYPE, 2; Familial hypertrophic cardiomyopathy 10; MYL2-Related Familial Hypertrophic Cardiomyopathy
Identifiers:: MONDO: MONDO:0012112; MedGen: C1834460; OMIM: 608758

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002296320	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 23, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24793961, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002296320

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 23, 2021)

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

Characterization of a phenotype-based genetic test prediction score for unrelated patients with hypertrophic cardiomyopathy.

Bos JM, Will ML, Gersh BJ, Kruisselbrink TM, Ommen SR, Ackerman MJ.

Mayo Clin Proc. 2014 Jun;89(6):727-37. doi: 10.1016/j.mayocp.2014.01.025. Epub 2014 May 1.

PubMed [citation]

PMID:: 24793961
PMCID:: PMC4234122

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002296320.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 24793961). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 166 of the MYL2 protein (p.Asp166His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine.

#	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: Feb 20, 2024

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