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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial restrictive, 3; Cardiomyopathy, dilated, 1D; Left ventricular noncompaction 6; Cardiomyopathy, familial hypertrophic, 2	AD	Cardiovascular	Preventive measures, surveillance (eg, including echocardiography and electrocardiography), and medical management may be helpful to help decrease morbidity	Cardiovascular	7981753; 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.

• not provided (8 variants)
• Hypertrophic cardiomyopathy 2 (7 variants)
• Dilated cardiomyopathy 1D (7 variants)
• Cardiomyopathy, familial restrictive, 3 (6 variants)
• Cardiomyopathy (5 variants)
• Cardiovascular phenotype (4 variants)
• Hypertrophic cardiomyopathy (3 variants)
• Dilated cardiomyopathy 1D;Cardiomyopathy, familial restrictive, 3;Hypertrophic cardiomyopathy 2 (2 variants)
• Hypertrophic cardiomyopathy 2;Dilated cardiomyopathy 1D;Cardiomyopathy, familial restrictive, 3 (2 variants)
• Primary dilated cardiomyopathy (2 variants)
• Primary familial hypertrophic cardiomyopathy (2 variants)
• Familial isolated dilated cardiomyopathy (1 variants)
• Cardiomyopathy, familial restrictive, 3;Dilated cardiomyopathy 1D;Hypertrophic cardiomyopathy 2 (1 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)
• Dilated cardiomyopathy 1D;Hypertrophic cardiomyopathy 2;Cardiomyopathy, familial restrictive, 3 (1 variants)
• TNNT2 -related cardiomyopathies (1 variants)
• Primary dilated cardiomyopathy;Hypertrophic cardiomyopathy (1 variants)
• beta Thalassemia (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	123		124
missense	11	37	290	2	1	341
nonsense		2	14			16
start loss			1			1
frameshift	1	1	11			13
inframe indel	1	2	9			12
splice donor/acceptor (+/-2bp)		7	21			28
splice region			42	41	6	89
non coding			24	129	56	209
Total	13	49	371	254	57

Highest pathogenic variant AF is 0.0000197

Variants in TNNT2

This is a list of pathogenic ClinVar variants found in the TNNT2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-201359030-T-A			Benign (Mar 03, 2015)
1-201359040-G-C			Benign (Mar 03, 2015)
1-201359060-G-A			Benign (Mar 03, 2015)
1-201359087-G-A			Benign (Mar 03, 2015)
1-201359119-TG-T			Benign (Mar 03, 2015)
1-201359122-G-C			Benign (Mar 03, 2015)
1-201359139-G-A			Benign (Mar 03, 2015)
1-201359144-C-T		Left ventricular noncompaction cardiomyopathy • Hypertrophic cardiomyopathy • Dilated Cardiomyopathy, Dominant • Familial restrictive cardiomyopathy • Dilated cardiomyopathy 1D • Hypertrophic cardiomyopathy 2 • Cardiomyopathy, familial restrictive, 3	Benign/Likely benign (Apr 11, 2023)
1-201359170-T-G			Benign (Mar 03, 2015)
1-201359171-G-A		Hypertrophic cardiomyopathy 2 • Cardiomyopathy, familial restrictive, 3	Conflicting classifications of pathogenicity (Jan 13, 2018)
1-201359173-G-A		Dilated cardiomyopathy 1D • Hypertrophic cardiomyopathy 2 • Cardiomyopathy, familial restrictive, 3	Conflicting classifications of pathogenicity (Oct 01, 2023)
1-201359173-G-C		Hypertrophic cardiomyopathy 2 • Cardiomyopathy, familial restrictive, 3 • Dilated cardiomyopathy 1D	Uncertain significance (Jan 13, 2018)
1-201359178-AG-A			Benign (Mar 03, 2015)
1-201359207-G-C		Cardiomyopathy	Uncertain significance (Jul 13, 2020)
1-201359207-G-T		Cardiomyopathy	Conflicting classifications of pathogenicity (Jul 14, 2020)
1-201359208-C-T		Cardiomyopathy	Uncertain significance (Sep 09, 2023)
1-201359210-C-T		Dilated cardiomyopathy 1D;Cardiomyopathy, familial restrictive, 3;Hypertrophic cardiomyopathy 2 • Cardiovascular phenotype • Cardiomyopathy, familial restrictive, 3 • Dilated cardiomyopathy 1D • Hypertrophic cardiomyopathy 2 • Cardiomyopathy	Likely benign (Nov 30, 2023)
1-201359212-A-G		Cardiovascular phenotype	Uncertain significance (Nov 19, 2019)
1-201359214-T-G		Hypertrophic cardiomyopathy 2;Cardiomyopathy, familial restrictive, 3;Dilated cardiomyopathy 1D	Uncertain significance (Dec 08, 2016)
1-201359216-C-G		Hypertrophic cardiomyopathy 2;Dilated cardiomyopathy 1D;Cardiomyopathy, familial restrictive, 3	Uncertain significance (Dec 06, 2023)
1-201359216-C-T		Hypertrophic cardiomyopathy • Dilated cardiomyopathy 1D;Cardiomyopathy, familial restrictive, 3;Hypertrophic cardiomyopathy 2 • Cardiovascular phenotype • Hypertrophic cardiomyopathy 2 • Dilated cardiomyopathy 1D • Cardiomyopathy, familial restrictive, 3	Pathogenic/Likely pathogenic (Jan 08, 2024)
1-201359217-C-A		Cardiomyopathy	Uncertain significance (Jan 11, 2024)
1-201359217-C-T		Hypertrophic cardiomyopathy 2 • Primary familial hypertrophic cardiomyopathy • Hypertrophic cardiomyopathy • Dilated cardiomyopathy 1D;Cardiomyopathy, familial restrictive, 3;Hypertrophic cardiomyopathy 2 • Cardiomyopathy • Dilated cardiomyopathy 1D • Cardiovascular phenotype • Cardiomyopathy, familial restrictive, 3	Pathogenic/Likely pathogenic (Jan 11, 2024)
1-201359220-C-T		not specified • Primary familial hypertrophic cardiomyopathy • Cardiovascular phenotype • Hypertrophic cardiomyopathy 2;Dilated cardiomyopathy 1D;Cardiomyopathy, familial restrictive, 3 • Cardiomyopathy • Dilated cardiomyopathy 1D • Cardiomyopathy, familial restrictive, 3 • Hypertrophic cardiomyopathy 2	Uncertain significance (Apr 18, 2024)
1-201359221-G-A		Hypertrophic cardiomyopathy 1 • Hypertrophic cardiomyopathy • Cardiomyopathy, familial restrictive, 3;Dilated cardiomyopathy 1D;Hypertrophic cardiomyopathy 2 • Cardiovascular phenotype • Cardiomyopathy • Hypertrophic cardiomyopathy 2	Conflicting classifications of pathogenicity (Dec 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNNT2	protein_coding	protein_coding	ENST00000509001	15	18755

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00200	0.997	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	121	164	0.738	0.0000109	1919
Missense in Polyphen		44	66.392	0.66273		682
Synonymous	0.0617	56	56.6	0.990	0.00000356	460
Loss of Function	2.92	9	24.6	0.365	0.00000135	296

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

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
• gene_indispensability_pred: E
• gene_indispensability_score: 0.859

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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