NM_024334.3(TMEM43):c.1021C>T (p.Arg341Ter) AND Arrhythmogenic right ventricular cardiomyopathy, type 5

Clinical significance:Uncertain significance (Last evaluated: Sep 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001326745.1

Allele description [Variation Report for NM_024334.3(TMEM43):c.1021C>T (p.Arg341Ter)]

NM_024334.3(TMEM43):c.1021C>T (p.Arg341Ter)

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.1021C>T (p.Arg341Ter)
HGVS:
  • NC_000003.12:g.14141613C>T
  • NG_008975.1:g.21674C>T
  • NM_024334.3:c.1021C>TMANE SELECT
  • NP_077310.1:p.Arg341Ter
  • NP_077310.1:p.Arg341Ter
  • LRG_435t1:c.1021C>T
  • LRG_435:g.21674C>T
  • LRG_435p1:p.Arg341Ter
  • NC_000003.11:g.14183113C>T
  • NM_024334.2:c.1021C>T
Protein change:
R341*
Links:
dbSNP: rs778127887
NCBI 1000 Genomes Browser:
rs778127887
Molecular consequence:
  • NM_024334.3:c.1021C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy, type 5 (ARVD5)
Synonyms:
ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 5; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 5
Identifiers:
MONDO: MONDO:0011459; MedGen: C1858379; OMIM: 604400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001517792Invitaecriteria provided, single submitter
Uncertain significance
(Sep 13, 2020)
germlineclinical testing

PubMed (4)
[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

Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene.

Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, Kupprion C, Ramadanova K, Thierfelder L, McKenna W, Gallagher B, Morris-Larkin L, Bassett AS, Parfrey PS, Young TL.

Am J Hum Genet. 2008 Apr;82(4):809-21. doi: 10.1016/j.ajhg.2008.01.010. Epub 2008 Feb 28.

PubMed [citation]
PMID:
18313022
PMCID:
PMC2427209

TMEM43 mutations associated with arrhythmogenic right ventricular cardiomyopathy in non-Newfoundland populations.

Baskin B, Skinner JR, Sanatani S, Terespolsky D, Krahn AD, Ray PN, Scherer SW, Hamilton RM.

Hum Genet. 2013 Nov;132(11):1245-52. doi: 10.1007/s00439-013-1323-2. Epub 2013 Jun 29.

PubMed [citation]
PMID:
23812740
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001517792.1

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

Description

This sequence change results in a premature translational stop signal in the last exon of the TMEM43 mRNA at codon 341 (p.Arg341*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 60 amino acids of the TMEM43 protein. This variant is present in population databases (rs778127887, ExAC 0.02%) but has not been reported in the literature in individuals with a TMEM43-related disease. ClinVar contains an entry for this variant (Variation ID: 217494). This variant would result in the deletion of the C-terminus region of the TMEM43 protein, that includes missense variants reported in individuals affected with arrhythmogenic right ventricular cardiomyopathy. One of these variants (p.Ser358Leu) has been demonstrated to be deleterious (PMID: 18313022, 23812740, 25343256), suggesting that loss of the C-terminal region of TMEM43 is detrimental for protein function. In summary, this variant is a rare nonsense variant that is expected to delete a region of the TMEM43 protein that may be important for protein function. However, in the absence of confirmed segregation or functional studies, at this time this change has been classified as a Variant of Uncertain Significance.

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

Last Updated: Dec 4, 2021

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