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NM_001276345.2(TNNT2):c.311G>T (p.Arg104Leu) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 29, 2018
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:
RCV000619398.2

Allele description

NM_001276345.2(TNNT2):c.311G>T (p.Arg104Leu)

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.311G>T (p.Arg104Leu)
Other names:
p.R94L:CGC>CTC
HGVS:
  • NC_000001.11:g.201365291C>A
  • NG_007556.1:g.17387G>T
  • NM_000364.4:c.311G>T
  • NM_001001430.3:c.281G>T
  • NM_001001431.3:c.281G>T
  • NM_001001432.3:c.266G>T
  • NM_001276345.2:c.311G>TMANE SELECT
  • NM_001276346.2:c.291+319G>T
  • NM_001276347.2:c.281G>T
  • NP_000355.2:p.Arg104Leu
  • NP_001001430.1:p.Arg94Leu
  • NP_001001431.1:p.Arg94Leu
  • NP_001001432.1:p.Arg89Leu
  • NP_001263274.1:p.Arg104Leu
  • NP_001263276.1:p.Arg94Leu
  • LRG_431t1:c.311G>T
  • LRG_431:g.17387G>T
  • LRG_431p1:p.Arg104Leu
  • NC_000001.10:g.201334419C>A
  • NM_001001430.1:c.281G>T
  • NM_001001430.2:c.281G>T
  • NM_001276346.1:c.291+319G>T
  • c.281G>T
Protein change:
R104L
Links:
dbSNP: rs397516457
NCBI 1000 Genomes Browser:
rs397516457
Molecular consequence:
  • NM_001276346.2:c.291+319G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000364.4:c.311G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.281G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.281G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.266G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.311G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.281G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000740033Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Jan 29, 2018) 		germlineclinical testing

PubMed (13)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

A new mutation of the cardiac troponin T gene causing familial hypertrophic cardiomyopathy without left ventricular hypertrophy.

Varnava A, Baboonian C, Davison F, de Cruz L, Elliott PM, Davies MJ, McKenna WJ.

Heart. 1999 Nov;82(5):621-4.

PubMed [citation]
PMID:
10525521
PMCID:
PMC1760789

Cytosine methylation confers instability on the cardiac troponin T gene in hypertrophic cardiomyopathy.

D'Cruz LG, Baboonian C, Phillimore HE, Taylor R, Elliott PM, Varnava A, Davison F, McKenna WJ, Carter ND.

J Med Genet. 2000 Sep;37(9):E18. No abstract available.

PubMed [citation]
PMID:
10978365
PMCID:
PMC1734704
See all PubMed Citations (13)

Details of each submission

From Ambry Genetics, SCV000740033.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (13)

Description

The p.R94L pathogenic mutation (also known as c.281G>T), located in coding exon 8 of the TNNT2 gene, results from a G to T substitution at nucleotide position 281. The arginine at codon 94 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported in several hypertrophic cardiomyopathy (HCM) cohorts and has been shown to segregate with disease in one small family (Varnava A et al. Heart. 1999;82:621-4; Melacini P et al. Eur Heart J. 2010 Sep;31(17):2111-23; Pasquale F et al. Circ Cardiovasc Genet. 2012 Feb;5(1):10-7). Functional in vitro analyses involving skinned cardiac fibers have suggested that this alteration affects TNNT2 protein function (Lu QW et al. J Mol Cell Cardiol. 2003;35:1421-7). In addition, alterations involving the same amino acid, p.R94C (c.280C>T) and p.R94H (c.281G>A), have been described in patients with HCM including de novo occurrences (D'Cruz LG et al. J Med Genet. 2000;37:E18; Millat G et al. Eur J Med Genet. 2010;53:261-7). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Apr 20, 2024