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NM_000258.3(MYL3):c.427G>A (p.Glu143Lys) AND MYL3-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 27, 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:
RCV003407333.5

Allele description [Variation Report for NM_000258.3(MYL3):c.427G>A (p.Glu143Lys)]

NM_000258.3(MYL3):c.427G>A (p.Glu143Lys)

Gene:
MYL3:myosin light chain 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.31
Genomic location:
Preferred name:
NM_000258.3(MYL3):c.427G>A (p.Glu143Lys)
Other names:
p.E143K:GAG>AAG
HGVS:
  • NC_000003.12:g.46859529C>T
  • NG_007555.2:g.27641G>A
  • NM_000258.3:c.427G>AMANE SELECT
  • NP_000249.1:p.Glu143Lys
  • NP_000249.1:p.Glu143Lys
  • LRG_395t1:c.427G>A
  • LRG_395:g.27641G>A
  • LRG_395p1:p.Glu143Lys
  • NC_000003.11:g.46901019C>T
  • NM_000258.2:c.427G>A
  • P08590:p.Glu143Lys
  • c.427G>A
  • p.(Glu143Lys)
Protein change:
E143K; GLU143LYS
Links:
Leiden Muscular Dystrophy (MYL3): MYL3_00009; UniProtKB: P08590#VAR_019843; OMIM: 160790.0003; dbSNP: rs104893750
NCBI 1000 Genomes Browser:
rs104893750
Molecular consequence:
  • NM_000258.3:c.427G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
functional variant [Sequence Ontology: SO:0001536]

Condition(s)

Name:
MYL3-related disorder
Synonyms:
MYL3-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004114327PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jan 27, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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 PreventionGenetics, part of Exact Sciences, SCV004114327.1

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

Description

The MYL3 c.427G>A variant is predicted to result in the amino acid substitution p.Glu143Lys. This variant has been reported in many individuals affected with hypertrophic cardiomyopathy (HCM) (Walsh R et al 2016. PubMed ID: 27532257; Gómez J et al 2017. PubMed ID: 28356264; McNamara JW et al 2017. PubMed ID: 28658286; Mademont-Soler I et al 2017. PubMed ID: 28771489; Yadav S et al 2019. PubMed ID: 30706179; Miller RJH et al 2019. PubMed ID: 31199839; Yoneda ZT et al 2021. PubMed ID: 34495297). In at least two families, this variant was reported as homozygotes in the affected individuals with restrictive cardiomyopathy whereas heterozygous carriers were clinically unaffected (Olson et al 2002. PubMed ID: 12021217; Caleshu C et al 2011. PubMed ID: 21823217). Functional studies suggested this variant reduces the binding affinity for the cardiac myosin heavy chain, and transgenic mice overexpressing the p.Glu413Lys variant exhibit clinical features of restrictive cardiomyopathy (Lossie J et al 2011. PubMed ID: 22131351; Sahni N et al 2015. PubMed ID: 25910212; Yuan CC et al 2017. PubMed ID: 28371863). This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-46901019-C-T). This variant is interpreted as likely pathogenic.

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

Last Updated: Sep 29, 2024