NM_001276345.2(TNNT2):c.460C>T (p.Arg154Trp) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jun 28, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000612990.2

Allele description [Variation Report for NM_001276345.2(TNNT2):c.460C>T (p.Arg154Trp)]

NM_001276345.2(TNNT2):c.460C>T (p.Arg154Trp)

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.460C>T (p.Arg154Trp)
Other names:
R144W(missense/non-synonymousmutation)
HGVS:
  • NC_000001.11:g.201364327G>A
  • NG_007556.1:g.18351C>T
  • NM_000364.4:c.460C>T
  • NM_001001430.3:c.430C>T
  • NM_001001431.3:c.430C>T
  • NM_001001432.3:c.415C>T
  • NM_001276345.2:c.460C>TMANE SELECT
  • NM_001276346.2:c.340C>T
  • NM_001276347.2:c.430C>T
  • NP_000355.2:p.Arg154Trp
  • NP_001001430.1:p.Arg144Trp
  • NP_001001431.1:p.Arg144Trp
  • NP_001001432.1:p.Arg139Trp
  • NP_001263274.1:p.Arg154Trp
  • NP_001263275.1:p.Arg114Trp
  • NP_001263276.1:p.Arg144Trp
  • LRG_431t1:c.460C>T
  • LRG_431:g.18351C>T
  • LRG_431p1:p.Arg154Trp
  • NC_000001.10:g.201333455G>A
  • NM_001001430.1:c.430C>T
  • NM_001001430.2:c.430C>T
Protein change:
R114W
Links:
dbSNP: rs483352832
NCBI 1000 Genomes Browser:
rs483352832
Molecular consequence:
  • NM_000364.4:c.460C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001430.3:c.430C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001431.3:c.430C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001001432.3:c.415C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276345.2:c.460C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276346.2:c.340C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276347.2:c.430C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000713432Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Jun 28, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown11not providednot providednot providedclinical testing

Citations

PubMed

A novel arginine to tryptophan (R144W) mutation in troponin T (cTnT) gene in an indian multigenerational family with dilated cardiomyopathy (FDCM).

Rani DS, Dhandapany PS, Nallari P, Narasimhan C, Thangaraj K.

PLoS One. 2014;9(7):e101451. doi: 10.1371/journal.pone.0101451.

PubMed [citation]
PMID:
24992688
PMCID:
PMC4081629

Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.

Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubbenhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL.

Am J Hum Genet. 2016 May 5;98(5):801-817. doi: 10.1016/j.ajhg.2016.02.024.

PubMed [citation]
PMID:
27153395
PMCID:
PMC4863474
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000713432.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg144Trp variant in TNNT2 has been reported in 1 individual with dilated cardiomyopathy and segregated with disease in 4 affected relatives, including 1 obligate carrier (Rani 2014). It has also been identified in 4/30504 South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org/) and has been reported in ClinVar (Variation ID #132943). An in vitro functional study suggests that this variant may disrupt troponin binding (Gangadharan 2017) and computational prediction tools suggest that it may impact the protein, though this information is not predictive enough to determine pathogenicity.In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria Applied: PS3_Supporting, PP1, PP3.

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

Last Updated: Jul 13, 2021

Support Center