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NM_000432.4(MYL2):c.64G>A (p.Glu22Lys) AND Cardiomyopathy

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Mar 21, 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:
RCV001170438.11

Allele description [Variation Report for NM_000432.4(MYL2):c.64G>A (p.Glu22Lys)]

NM_000432.4(MYL2):c.64G>A (p.Glu22Lys)

Genes:
LOC114827850:VISTA enhancer hs2149 [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.64G>A (p.Glu22Lys)
Other names:
p.E22K:GAA>AAA
HGVS:
  • NC_000012.12:g.110919133C>T
  • NG_007554.1:g.6445G>A
  • NG_065206.1:g.281C>T
  • NM_000432.4:c.64G>AMANE SELECT
  • NP_000423.2:p.Glu22Lys
  • NP_000423.2:p.Glu22Lys
  • LRG_393t1:c.64G>A
  • LRG_393:g.6445G>A
  • LRG_393p1:p.Glu22Lys
  • NC_000012.11:g.111356937C>T
  • NM_000432.3:c.64G>A
  • P10916:p.Glu22Lys
  • p.(Glu22Lys)
Protein change:
E22K; GLU22LYS
Links:
Leiden Muscular Dystrophy (MYL2): MYL2_00003; UniProtKB: P10916#VAR_004603; OMIM: 160781.0002; dbSNP: rs104894368
NCBI 1000 Genomes Browser:
rs104894368
Molecular consequence:
  • NM_000432.4:c.64G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
probably has functional consequence

Condition(s)

Name:
Cardiomyopathy (CMYO)
Synonyms:
Cardiomyopathies
Identifiers:
MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001333018CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Mar 28, 2022)
germlineclinical testing

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

SCV001351143Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 21, 2023)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli.

Hughes JM, Murad F, Chang B, Guerrant RL.

Nature. 1978 Feb 23;271(5647):755-6. No abstract available.

PubMed [citation]
PMID:
203862

Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle.

Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND.

Nat Genet. 1996 May;13(1):63-9.

PubMed [citation]
PMID:
8673105
See all PubMed Citations (11)

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV001333018.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV001351143.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This missense variant replaces glutamic acid with lysine at codon 22 of the MYL2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant affects protein function by altering calcium sensitivity of force and ATPase activity in vitro and in transgenic mice (PMID: 12668451, 14594949, 16076902, 17606808, 25324513). This variant has been reported in over 40 individuals affected with hypertrophic cardiomyopathy from over 20 families (PMID: 8673105, 12404107, 26497160, 27532257; ClinVar SCV000203862.4). This variant has shown reduced penetrance and late-onset disease with moderate symptoms in some individuals. A study of 38 carriers from 14 Dutch families has suggested that this variant together with the presence of an additional risk factor, such as hypertension, contributes to the development of hypertrophic cardiomyopathy (PMID: 26497160). This variant has been identified in 5/251472 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2024