Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_001276345.2(TNNT2):c.305G>A (p.Arg102Gln)

Help
Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Sep 30, 2021)
Last evaluated:
Aug 20, 2020
Accession:
VCV000012409.11
Variation ID:
12409
Description:
single nucleotide variant
Help

NM_001276345.2(TNNT2):c.305G>A (p.Arg102Gln)

Allele ID
27448
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q32.1
Genomic location
1: 201365297 (GRCh38) GRCh38 UCSC
1: 201334425 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.201334425C>T
NC_000001.11:g.201365297C>T
NG_007556.1:g.17381G>A
... more HGVS
Protein change
R92Q, R102Q, R87Q
Other names
p.R92Q:CGG>CAG
Canonical SPDI
NC_000001.11:201365296:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA004273
OMIM: 191045.0002
dbSNP: rs121964856
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, single submitter Mar 8, 2016 RCV000013220.24
Pathogenic 4 criteria provided, single submitter Apr 27, 2018 RCV000159281.7
Pathogenic 1 criteria provided, single submitter Jul 10, 2018 RCV000211865.2
Pathogenic 1 criteria provided, single submitter Jun 13, 2017 RCV000621709.1
Pathogenic 1 criteria provided, single submitter Aug 20, 2020 RCV000627784.5
Help
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
595 610

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jul 10, 2018)
criteria provided, single submitter
Method: clinical testing
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000060229.6
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (17)
Comment:
The p.Arg92Gln variant in TNNT2 has been reported in >15 individuals with HCM, i ncluding one de novo occurrence, and segregated with disease in >15 … (more)
Pathogenic
(Jun 13, 2017)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000735554.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (15)
Comment:
The p.R92Q pathogenic mutation (also known as c.275G>A), located in coding exon 8 of the TNNT2 gene, results from a G to A substitution at … (more)
Pathogenic
(Aug 20, 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: SCV000285648.8
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (19)
Comment:
This sequence change replaces arginine with glutamine at codon 92 of the TNNT2 protein (p.Arg92Gln). The arginine residue is highly conserved and there is a … (more)
Likely pathogenic
(Mar 08, 2016)
criteria provided, single submitter
Method: clinical testing
Familial hypertrophic cardiomyopathy 2
Allele origin: germline
Center for Medical Genetics Ghent,University of Ghent
Accession: SCV000299242.2
Submitted: (Jun 11, 2018)
Evidence details
Publications
PubMed (1)
Comment:
This variant has not been identified in large population databases (Gnomad, 1000 Genomes, Go NL, Exome Variant Server) and is predicted to have an impact … (more)
Pathogenic
(Apr 27, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000209227.11
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R92Q variant in the TNNT2 gene has been published multiple times in association with HCM (Theirfelder L et al., 1994; Yanaga F et al., … (more)
Pathogenic
(Jan 16, 2012)
no assertion criteria provided
Method: clinical testing
Not provided
Allele origin: germline
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280516.1
Submitted: (May 06, 2016)
Evidence details
Comment:
Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case … (more)
Pathogenic
(Jun 03, 1994)
no assertion criteria provided
Method: literature only
CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 2
Allele origin: germline
OMIM
Accession: SCV000033467.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics,Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001917971.1
Submitted: (Sep 23, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953929.1
Submitted: (Sep 30, 2021)
Evidence details

Functional evidence

Help
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

Help
Title Author Journal Year Link
Pathogenesis of Hypertrophic Cardiomyopathy is Mutation Rather Than Disease Specific: A Comparison of the Cardiac Troponin T E163R and R92Q Mouse Models. Ferrantini C Journal of the American Heart Association 2017 PMID: 28735292
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Walsh R Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 27532257
Clinical and Prognostic Profiles of Cardiomyopathies Caused by Mutations in the Troponin T Gene. Ripoll-Vera T Revista espanola de cardiologia (English ed.) 2016 PMID: 26507537
Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Lopes LR Heart (British Cardiac Society) 2015 PMID: 25351510
A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction. Tian T Heart and vessels 2015 PMID: 24691700
Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations. Coppini R Journal of the American College of Cardiology 2014 PMID: 25524337
Early results of sarcomeric gene screening from the Egyptian National BA-HCM Program. Kassem HSh Journal of cardiovascular translational research 2013 PMID: 23233322
Disease-related cardiac troponins alter thin filament Ca2+ association and dissociation rates. Liu B PloS one 2012 PMID: 22675533
Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T gene. Pasquale F Circulation. Cardiovascular genetics 2012 PMID: 22144547
IMAGE CARDIO MED: Inducible malignant ventricular tachyarrhythmia in a patient with genotyped hypertrophic cardiomyopathy in absence of left ventricular hypertrophy or enlargement. Ariyarajah V Circulation 2009 PMID: 19487599
[Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy]. García-Castro M Revista espanola de cardiologia 2009 PMID: 19150014
Late gadolinium enhancement cardiovascular magnetic resonance in genotyped hypertrophic cardiomyopathy with normal phenotype. Strijack B Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 2008 PMID: 19087273
Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. Olivotto I Mayo Clinic proceedings 2008 PMID: 18533079
Shared genetic causes of cardiac hypertrophy in children and adults. Morita H The New England journal of medicine 2008 PMID: 18403758
Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments. Robinson P Circulation research 2007 PMID: 17932326
Changes in the chemical and dynamic properties of cardiac troponin T cause discrete cardiomyopathies in transgenic mice. Ertz-Berger BR Proceedings of the National Academy of Sciences of the United States of America 2005 PMID: 16326803
Prevalence and clinical profile of troponin T mutations among patients with hypertrophic cardiomyopathy in tuscany. Torricelli F The American journal of cardiology 2003 PMID: 14636924
Alterations in thin filament regulation induced by a human cardiac troponin T mutant that causes dilated cardiomyopathy are distinct from those induced by troponin T mutants that cause hypertrophic cardiomyopathy. Robinson P The Journal of biological chemistry 2002 PMID: 12186860
Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region. Palm T Biophysical journal 2001 PMID: 11606294
Ca(2+) activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T. Chandra M American journal of physiology. Heart and circulatory physiology 2001 PMID: 11158969
Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy. Tardiff JC The Journal of clinical investigation 1999 PMID: 10449439
Ca2+ sensitization and potentiation of the maximum level of myofibrillar ATPase activity caused by mutations of troponin T found in familial hypertrophic cardiomyopathy. Yanaga F The Journal of biological chemistry 1999 PMID: 10085122
Dominant-negative effect of a mutant cardiac troponin T on cardiac structure and function in transgenic mice. Oberst L The Journal of clinical investigation 1998 PMID: 9788962
Expression of a mutant (Arg92Gln) human cardiac troponin T, known to cause hypertrophic cardiomyopathy, impairs adult cardiac myocyte contractility. Marian AJ Circulation research 1997 PMID: 9201030
Sudden death due to troponin T mutations. Moolman JC Journal of the American College of Cardiology 1997 PMID: 9060892
Clinical manifestations of hypertrophic cardiomyopathy with mutations in the cardiac beta-myosin heavy chain gene or cardiac troponin T gene. Koga Y Journal of cardiac failure 1996 PMID: 8951566
Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. Watkins H The New England journal of medicine 1995 PMID: 7898523
Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Thierfelder L Cell 1994 PMID: 8205619

Text-mined citations for rs121964856...

Help
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 Oct 02, 2021