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NM_001276345.2(TNNT2):c.418C>T (p.Arg140Cys) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 27, 2015
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:
RCV000243733.3

Allele description [Variation Report for NM_001276345.2(TNNT2):c.418C>T (p.Arg140Cys)]

NM_001276345.2(TNNT2):c.418C>T (p.Arg140Cys)

Gene:
TNNT2:troponin T2, cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.1
Genomic location:
Preferred name:
NM_001276345.2(TNNT2):c.418C>T (p.Arg140Cys)
Other names:
p.R130C:CGT>TGT
HGVS:
  • NC_000001.11:g.201364369G>A
  • NG_007556.1:g.18309C>T
  • NM_000364.4:c.418C>T
  • NM_001001430.3:c.388C>T
  • NM_001001431.3:c.388C>T
  • NM_001001432.3:c.373C>T
  • NM_001276345.2:c.418C>TMANE SELECT
  • NM_001276346.2:c.298C>T
  • NM_001276347.2:c.388C>T
  • NP_000355.2:p.Arg140Cys
  • NP_001001430.1:p.Arg130Cys
  • NP_001001431.1:p.Arg130Cys
  • NP_001001432.1:p.Arg125Cys
  • NP_001263274.1:p.Arg140Cys
  • NP_001263275.1:p.Arg100Cys
  • NP_001263276.1:p.Arg130Cys
  • LRG_431t1:c.418C>T
  • LRG_431:g.18309C>T
  • LRG_431p1:p.Arg140Cys
  • NC_000001.10:g.201333497G>A
  • NM_000364.3:c.418C>T
  • NM_001001430.1:c.388C>T
  • NM_001001430.2:c.388C>T
  • NM_001001430.3:c.388C>T
  • c.388C>T
Protein change:
R100C
Links:
dbSNP: rs397516463
NCBI 1000 Genomes Browser:
rs397516463
Molecular consequence:
  • NM_000364.4:c.418C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.373C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.418C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276346.2:c.298C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.388C>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
SCV000320661Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Nov 27, 2015) 		germlineclinical testing

PubMed (5)
[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

Prevalence and clinical profile of troponin T mutations among patients with hypertrophic cardiomyopathy in tuscany.

Torricelli F, Girolami F, Olivotto I, Passerini I, Frusconi S, Vargiu D, Richard P, Cecchi F.

Am J Cardiol. 2003 Dec 1;92(11):1358-62.

PubMed [citation]
PMID:
14636924

Familial hypertrophic cardiomyopathy mutations from different functional regions of troponin T result in different effects on the pH and Ca2+ sensitivity of cardiac muscle contraction.

Harada K, Potter JD.

J Biol Chem. 2004 Apr 9;279(15):14488-95. Epub 2004 Jan 12.

PubMed [citation]
PMID:
14722098
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000320661.7

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

Description

The p.R130C variant (also known as c.388C>T), located in coding exon 9 of the TNNT2 gene, results from a C to T substitution at nucleotide position 388. The arginine at codon 130 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been reported in individuals with hypertrophic cardiomyopathy (HCM) (Torricelli F, Am. J. Cardiol. 2003 Dec; 92(11):1358-62. This variant was seen in a four members of a Chinese family affected with HCM (Song L, Clin. Chim. Acta 2005 Jan; 351(1-2):209-16). This variant was also reported in two adolescent Japanese siblings with HCM but also in their unaffected mother; the siblings also carried a second TNNT2 alteration that was present in their father who was affected with HCM (Fujita E, Heart Vessels 2013 Nov; 28(6):785-94). This variant was also reported to co-occur with a missense alteration in MYBPC3 in a Chinese family (Zou Y, Mol. Biol. Rep. 2013 Jun; 40(6):3969-76). In vitro studies suggest this TNNT2 p.R130C alteration may impact calcium sensitivity (Harada K, J. Biol. Chem. 2004 Apr; 279(15):14488-95). This variant was previously reported in the SNPDatabase as rs397516463. This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024