NM_000432.4(MYL2):c.260G>A (p.Gly87Glu) AND Hypertrophic cardiomyopathy 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 17, 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:: RCV000692199.5

Allele description [Variation Report for NM_000432.4(MYL2):c.260G>A (p.Gly87Glu)]

NM_000432.4(MYL2):c.260G>A (p.Gly87Glu)

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.260G>A (p.Gly87Glu)

HGVS:

NC_000012.12:g.110914200C>T
NG_007554.1:g.11378G>A
NM_000432.4:c.260G>AMANE SELECT
NP_000423.2:p.Gly87Glu
NP_000423.2:p.Gly87Glu
LRG_393t1:c.260G>A
LRG_393:g.11378G>A
LRG_393p1:p.Gly87Glu
NC_000012.11:g.111352004C>T
NM_000432.3:c.260G>A

Protein change:

G87E

Links:

dbSNP: rs397516399

NCBI 1000 Genomes Browser:

rs397516399

Molecular consequence:

NM_000432.4:c.260G>A - 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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protein O-glucosyltransferase 1 isoform X1 [Orcinus orca]
protein O-glucosyltransferase 1 isoform X1 [Orcinus orca]
gi|466051992|ref|XP_004278565.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000820010	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23283745, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000820010

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 17, 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

Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy.

Zou Y, Wang J, Liu X, Wang Y, Chen Y, Sun K, Gao S, Zhang C, Wang Z, Zhang Y, Feng X, Song Y, Wu Y, Zhang H, Jia L, Wang H, Wang D, Yan C, Lu M, Zhou X, Song L, Hui R.

Mol Biol Rep. 2013 Jun;40(6):3969-76. doi: 10.1007/s11033-012-2474-2. Epub 2013 Jan 3.

PubMed [citation]

PMID:: 23283745

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000820010.4

#	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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 571147). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy but a variant in MYH7 was also identified in this individual (PMID: 23283745). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 87 of the MYL2 protein (p.Gly87Glu).

#	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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