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NM_024334.3(TMEM43):c.1073C>T (p.Ser358Leu) AND Arrhythmogenic right ventricular cardiomyopathy

Germline classification:
Pathogenic (3 submissions)
Last evaluated:
Oct 15, 2015
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:
RCV000039375.10

Allele description [Variation Report for NM_024334.3(TMEM43):c.1073C>T (p.Ser358Leu)]

NM_024334.3(TMEM43):c.1073C>T (p.Ser358Leu)

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.1073C>T (p.Ser358Leu)
Other names:
p.S358L:TCG>TTG
HGVS:
  • NC_000003.12:g.14141665C>T
  • NG_008975.1:g.21726C>T
  • NM_024334.3:c.1073C>TMANE SELECT
  • NP_077310.1:p.Ser358Leu
  • NP_077310.1:p.Ser358Leu
  • LRG_435t1:c.1073C>T
  • LRG_435:g.21726C>T
  • LRG_435p1:p.Ser358Leu
  • NC_000003.11:g.14183165C>T
  • NM_024334.2:c.1073C>T
  • Q9BTV4:p.Ser358Leu
  • c.1073C>T
  • p.S358L
Protein change:
S358L; SER358LEU
Links:
UniProtKB: Q9BTV4#VAR_044438; OMIM: 612048.0001; dbSNP: rs63750743
NCBI 1000 Genomes Browser:
rs63750743
Molecular consequence:
  • NM_024334.3:c.1073C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
9

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:
Cardiomyopathy, ARVC; Arrhythmogenic right ventricular dysplasia
Identifiers:
MONDO: MONDO:0016587; MedGen: C0349788

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000063059Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
no assertion criteria provided
Pathogenic
(Apr 4, 2015)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV000207271Blueprint Genetics
criteria provided, single submitter

(Variant Classification)
Pathogenic
(Oct 15, 2015)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV000987538Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenicgermlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlinenot provided279not providednot providednot providedclinical testing

Citations

PubMed

Functional effects of the TMEM43 Ser358Leu mutation in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy.

Rajkumar R, Sembrat JC, McDonough B, Seidman CE, Ahmad F.

BMC Med Genet. 2012 Mar 29;13:21. doi: 10.1186/1471-2350-13-21.

PubMed [citation]
PMID:
22458570
PMCID:
PMC3352248

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
See all PubMed Citations (7)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000063059.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided27not providednot providedclinical testing PubMed (5)

Description

The p.Ser358Leu variant in TMEM43 has been reported in >20 families with ARVC (a t least 15 from Newfoundland), including 1 de novo occurrence and segregated wit h disease in >20 affected relatives from these families (Merner 2008, Christense n 2011, Baskin 2013, Hodgkinson 2013, Milting 2014). It was absent from large po pulation studies. In summary, this variant meets criteria to be classified as pa thogenic for autosomal dominant ARVC. ACMG/AMP Criteria applied: PS4, PP1_Strong , PM2, PM6, PP3.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided27not provided9not provided

From Blueprint Genetics, SCV000207271.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV000987538.1

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

Last Updated: May 12, 2024