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NM_003673.4(TCAP):c.226C>T (p.Arg76Cys) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 11, 2022
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:
RCV002444746.3

Allele description [Variation Report for NM_003673.4(TCAP):c.226C>T (p.Arg76Cys)]

NM_003673.4(TCAP):c.226C>T (p.Arg76Cys)

Gene:
TCAP:titin-cap [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q12
Genomic location:
Preferred name:
NM_003673.4(TCAP):c.226C>T (p.Arg76Cys)
HGVS:
  • NC_000017.11:g.39665831C>T
  • NG_008892.1:g.5486C>T
  • NG_042278.1:g.2851C>T
  • NM_003673.4:c.226C>TMANE SELECT
  • NP_003664.1:p.Arg76Cys
  • NP_003664.1:p.Arg76Cys
  • LRG_210t1:c.226C>T
  • LRG_210:g.5486C>T
  • LRG_210p1:p.Arg76Cys
  • NC_000017.10:g.37822084C>T
  • NM_003673.3:c.226C>T
Protein change:
R76C
Links:
dbSNP: rs572836774
NCBI 1000 Genomes Browser:
rs572836774
Molecular consequence:
  • NM_003673.4:c.226C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002734007Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Oct 11, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

A mutation in telethonin alters Nav1.5 function.

Mazzone A, Strege PR, Tester DJ, Bernard CE, Faulkner G, De Giorgio R, Makielski JC, Stanghellini V, Gibbons SJ, Ackerman MJ, Farrugia G.

J Biol Chem. 2008 Jun 13;283(24):16537-44. doi: 10.1074/jbc.M801744200. Epub 2008 Apr 11. Erratum in: J Biol Chem. 2008 Aug 8;283(32):22336.

PubMed [citation]
PMID:
18408010
PMCID:
PMC2423252

Quantification of gastrointestinal sodium channelopathy.

Poh YC, Beyder A, Strege PR, Farrugia G, Buist ML.

J Theor Biol. 2012 Jan 21;293:41-8. doi: 10.1016/j.jtbi.2011.09.014. Epub 2011 Sep 21.

PubMed [citation]
PMID:
21959314
PMCID:
PMC3524340

Details of each submission

From Ambry Genetics, SCV002734007.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.R76C variant (also known as c.226C>T), located in coding exon 2 of the TCAP gene, results from a C to T substitution at nucleotide position 226. The arginine at codon 76 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was reported in one individual with intestinal pseudo-obstruction, and functional studies suggested some impact on sodium channel kinetics; however, cardiac details were not provided, and the clinical impact of experimental findings has not been determined (Mazzone A et al. J. Biol. Chem., 2008 Jun;283:16537-44; Poh YC et al. J. Theor. Biol., 2012 Jan;293:41-8). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Oct 20, 2024