GeneBe

TNNT2

troponin T2, cardiac type, the group of Troponin complex subunits

Basic information

Region (hg38): 1:201359008-201377764

Previous symbols: [ "CMH2", "CMD1D" ]

Links

ENSG00000118194 ∙ NCBI:7139 ∙ OMIM:191045 ∙ HGNC:11949 ∙ Uniprot:P45379 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • hypertrophic cardiomyopathy 2 (Strong), mode of inheritance: AD
  • dilated cardiomyopathy 1D (Definitive), mode of inheritance: AD
  • hypertrophic cardiomyopathy 2 (Definitive), mode of inheritance: AD
  • familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
  • left ventricular noncompaction (Supportive), mode of inheritance: AD
  • familial isolated restrictive cardiomyopathy (Supportive), mode of inheritance: AD
  • hypertrophic cardiomyopathy 3 (Definitive), mode of inheritance: AD
  • hypertrophic cardiomyopathy 2 (Definitive), mode of inheritance: AD
  • dilated cardiomyopathy 1D (Strong), mode of inheritance: AD
  • hypertrophic cardiomyopathy 2 (Strong), mode of inheritance: AD
  • cardiomyopathy, familial restrictive, 3 (Strong), mode of inheritance: AD
  • dilated cardiomyopathy (Definitive), mode of inheritance: AD
  • arrhythmogenic right ventricular cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD
  • hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
  • cardiomyopathy (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Cardiomyopathy, familial restrictive, 3; Cardiomyopathy, dilated, 1D; Left ventricular noncompaction 6; Cardiomyopathy, familial hypertrophic, 2ADCardiovascularPreventive measures, surveillance (eg, including echocardiography and electrocardiography), and medical management may be helpful to help decrease morbidityCardiovascular7981753; 8205619; 7898523; 9714088; 11106718; 11684629; 15542288; 16651346; 18506004; 18651846; 21483645; 21846512; 22144547; 22292720

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNNT2 gene.

  • Dilated_cardiomyopathy_1D (678 variants)
  • Hypertrophic_cardiomyopathy_2 (672 variants)
  • Cardiomyopathy,_familial_restrictive,_3 (666 variants)
  • Cardiomyopathy (380 variants)
  • not_provided (279 variants)
  • Cardiovascular_phenotype (240 variants)
  • not_specified (150 variants)
  • Hypertrophic_cardiomyopathy (45 variants)
  • Primary_dilated_cardiomyopathy (31 variants)
  • TNNT2-related_disorder (19 variants)
  • Primary_familial_hypertrophic_cardiomyopathy (16 variants)
  • Left_ventricular_noncompaction_cardiomyopathy (12 variants)
  • Dilated_Cardiomyopathy,_Dominant (10 variants)
  • Dilated_cardiomyopathy_1DD (5 variants)
  • Familial_restrictive_cardiomyopathy (5 variants)
  • Hypertrophic_cardiomyopathy_1 (4 variants)
  • Primary_familial_dilated_cardiomyopathy (4 variants)
  • See_cases (2 variants)
  • Supraventricular_tachycardia (1 variants)
  • Sudden_unexplained_death (1 variants)
  • Restrictive_cardiomyopathy (1 variants)
  • Left_ventricular_noncompaction (1 variants)
  • Autosomal_recessive_congenital_ichthyosis_1 (1 variants)
  • Left_ventricular_hypertrophy (1 variants)
  • Sudden_cardiac_death (1 variants)
  • Dilated_cardiomyopathy_1S (1 variants)
  • Increased_left_ventricular_wall_thickness (1 variants)
  • Hypertrophic_cardiomyopathy_4 (1 variants)
  • Familial_isolated_dilated_cardiomyopathy (1 variants)
  • Hypertrophic_cardiomyopathy_7 (1 variants)
  • Costello_syndrome (1 variants)
  • Hypokinetic_non-dilated_cardiomyopathy (1 variants)
  • Wolff-Parkinson-White_pattern (1 variants)
  • Myocarditis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNNT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001276345.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
143
clinvar
1
clinvar
 148
missense
17
clinvar
70
clinvar
347
clinvar
6
clinvar
2
clinvar
 442
nonsense
2
clinvar
16
clinvar
 18
start loss
1
1
 2
frameshift
1
clinvar
1
clinvar
18
clinvar
 20
splice donor/acceptor (+/-2bp)
11
clinvar
27
clinvar
 38
Total 18 85 413 149 3

Highest pathogenic variant AF is 0.000028748338

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TNNT2protein_codingprotein_codingENST00000509001 1518755
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.002000.9971257230251257480.0000994
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.191211640.7380.00001091919
Missense in Polyphen4466.3920.66273682
Synonymous0.06175656.60.9900.00000356460
Loss of Function2.92924.60.3650.00000135296

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001520.000152
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.0001760.000176
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.;
Disease
DISEASE: Cardiomyopathy, familial hypertrophic 2 (CMH2) [MIM:115195]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:10525521, ECO:0000269|PubMed:11034944, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:15563892, ECO:0000269|PubMed:16199542, ECO:0000269|PubMed:21846512, ECO:0000269|PubMed:7898523, ECO:0000269|PubMed:8205619, ECO:0000269|PubMed:8989109, ECO:0000269|PubMed:9060892, ECO:0000269|PubMed:9140840, ECO:0000269|PubMed:9482583, ECO:0000269|Ref.19}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1D (CMD1D) [MIM:601494]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:11106718, ECO:0000269|PubMed:11684629, ECO:0000269|PubMed:15542288, ECO:0000269|PubMed:15769782, ECO:0000269|PubMed:21846512}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial restrictive 3 (RCM3) [MIM:612422]: A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. {ECO:0000269|PubMed:16651346}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Cardiac Progenitor Differentiation;Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

pRec
0.437

Intolerance Scores

loftool
0.0823
rvis_EVS
-0.16
rvis_percentile_EVS
41.64

Haploinsufficiency Scores

pHI
0.252
hipred
Y
hipred_score
0.685
ghis
0.504

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
gene_indispensability_pred
E
gene_indispensability_score
0.859

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tnnt2
Phenotype
growth/size/body region phenotype; homeostasis/metabolism phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
tnnt2a
Affected structure
hematopoietic multipotent progenitor cell
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
skeletal muscle contraction;muscle contraction;regulation of heart contraction;muscle filament sliding;negative regulation of ATPase activity;positive regulation of ATPase activity;regulation of muscle filament sliding speed;sarcomere organization;protein heterooligomerization;response to calcium ion;actin crosslink formation;ventricular cardiac muscle tissue morphogenesis;cardiac muscle contraction
Cellular component
cytosol;troponin complex;striated muscle thin filament;sarcomere;cardiac myofibril;cardiac Troponin complex
Molecular function
actin binding;calcium ion binding;protein binding;tropomyosin binding;troponin C binding;protein binding, bridging;calcium-dependent ATPase activity;troponin I binding