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

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jul 4, 2021)
Last evaluated:
Apr 1, 2021
Accession:
VCV000132943.9
Variation ID:
132943
Description:
single nucleotide variant
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NM_001276345.2(TNNT2):c.460C>T (p.Arg154Trp)

Allele ID
136692
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q32.1
Genomic location
1: 201364327 (GRCh38) GRCh38 UCSC
1: 201333455 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.201333455G>A
NC_000001.11:g.201364327G>A
NM_001276345.2:c.460C>T MANE Select NP_001263274.1:p.Arg154Trp missense
... more HGVS
Protein change
R144W, R154W, R114W, R139W
Other names
R144W(missense/non-synonymousmutation)
Canonical SPDI
NC_000001.11:201364326:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00003
Exome Aggregation Consortium (ExAC) 0.00003
Links
ClinGen: CA004554
dbSNP: rs483352832
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Jun 28, 2019 RCV000612990.2
Uncertain significance 1 criteria provided, single submitter Sep 24, 2020 RCV000646060.3
Uncertain significance 1 criteria provided, single submitter Apr 1, 2021 RCV001531033.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Feb 3, 2020 RCV000777699.3
Pathogenic 1 no assertion criteria provided - RCV000119344.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TNNT2 No evidence available No evidence available GRCh38
GRCh37
566 581

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Aug 20, 2018)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Allele origin: germline
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario
Accession: SCV001333852.1
Submitted: (Mar 03, 2020)
Evidence details
Uncertain significance
(Jun 28, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000713432.3
Submitted: (Jun 03, 2020)
Evidence details
Publications
PubMed (3)
Comment:
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 … (more)
Uncertain significance
(Sep 24, 2020)
criteria provided, single submitter
Method: clinical testing
Familial restrictive cardiomyopathy 3
Familial hypertrophic cardiomyopathy 2
Left ventricular noncompaction 6
Allele origin: germline
Invitae
Accession: SCV000767817.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces arginine with tryptophan at codon 144 of the TNNT2 protein (p.Arg144Trp). The arginine residue is highly conserved and there is a … (more)
Uncertain significance
(Apr 01, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001745970.1
Submitted: (Jul 04, 2021)
Evidence details
Uncertain significance
(Feb 03, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiomyopathy
Allele origin: germline
Color Health, Inc
Accession: SCV000913632.2
Submitted: (May 19, 2020)
Comment:
This missense variant replaces arginine with tryptophan at codon 144 of the TNNT2 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
Evidence details
pathogenic
(-)
no assertion criteria provided
Method: not provided
not provided
Allele origin: germline
Evolutionary and Medical Genetics Laboratory, Centre for Cellular and Molecular Biology
Accession: SCV000154241.2
Submitted: (Dec 16, 2014)
Comment:
Present study of all the exons and exon-intron boundaries of cTnT in 147 DCM and 207 healthy controls, had revealed a total of 15 SNPs … (more)
Evidence details
Comment:
Converted during submission to Pathogenic.

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Molecular mechanisms and structural features of cardiomyopathy-causing troponin T mutants in the tropomyosin overlap region. Gangadharan B Proceedings of the National Academy of Sciences of the United States of America 2017 PMID: 28973951
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. Maxwell KN American journal of human genetics 2016 PMID: 27153395
A novel arginine to tryptophan (R144W) mutation in troponin T (cTnT) gene in an indian multigenerational family with dilated cardiomyopathy (FDCM). Rani DS PloS one 2014 PMID: 24992688

Text-mined citations for rs483352832...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 13, 2021