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NM_024334.3(TMEM43):c.718C>T (p.Arg240Cys) AND Cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 4, 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:
RCV000769156.7

Allele description [Variation Report for NM_024334.3(TMEM43):c.718C>T (p.Arg240Cys)]

NM_024334.3(TMEM43):c.718C>T (p.Arg240Cys)

Gene:
TMEM43:transmembrane protein 43 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p25.1
Genomic location:
Preferred name:
NM_024334.3(TMEM43):c.718C>T (p.Arg240Cys)
Other names:
p.R240C:CGT>TGT
HGVS:
  • NC_000003.12:g.14135170C>T
  • NG_008975.1:g.15231C>T
  • NM_024334.3:c.718C>TMANE SELECT
  • NP_077310.1:p.Arg240Cys
  • NP_077310.1:p.Arg240Cys
  • LRG_435t1:c.718C>T
  • LRG_435:g.15231C>T
  • LRG_435p1:p.Arg240Cys
  • NC_000003.11:g.14176670C>T
  • NM_024334.2:c.718C>T
Protein change:
R240C
Links:
dbSNP: rs367910936
NCBI 1000 Genomes Browser:
rs367910936
Molecular consequence:
  • NM_024334.3:c.718C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000900530CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 16, 2017) 		germlineclinical testing

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

SCV001352902Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 4, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise.

Kapplinger JD, Landstrom AP, Salisbury BA, Callis TE, Pollevick GD, Tester DJ, Cox MG, Bhuiyan Z, Bikker H, Wiesfeld AC, Hauer RN, van Tintelen JP, Jongbloed JD, Calkins H, Judge DP, Wilde AA, Ackerman MJ.

J Am Coll Cardiol. 2011 Jun 7;57(23):2317-27. doi: 10.1016/j.jacc.2010.12.036.

PubMed [citation]
PMID:
21636032
PMCID:
PMC6311127

Remodeling of the cardiac sodium channel, connexin43, and plakoglobin at the intercalated disk in patients with arrhythmogenic cardiomyopathy.

Noorman M, Hakim S, Kessler E, Groeneweg JA, Cox MG, Asimaki A, van Rijen HV, van Stuijvenberg L, Chkourko H, van der Heyden MA, Vos MA, de Jonge N, van der Smagt JJ, Dooijes D, Vink A, de Weger RA, Varro A, de Bakker JM, Saffitz JE, Hund TJ, Mohler PJ, Delmar M, et al.

Heart Rhythm. 2013 Mar;10(3):412-9. doi: 10.1016/j.hrthm.2012.11.018. Epub 2012 Nov 23.

PubMed [citation]
PMID:
23178689
PMCID:
PMC3608196
See all PubMed Citations (4)

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository, SCV000900530.1

#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, SCV001352902.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This missense variant replaces arginine with cysteine at codon 240 of the TMEM43 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual with arrhythmogenic right ventricular cardiomyopathy, who also carried a pathogenic deletion of exons 1-14 of the PKP2 gene (PMID: 21636032, 23178689, 25820315), which suggests that this missense variant was probably not the primary cause of disease in this individual. This variant has been identified in 48/281274 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Apr 20, 2024