TNNT2

Chr 1AD

troponin T2, cardiac type

Also known as: CMD1D, CMH2, CMPD2, LVNC6, RCM3, TnTC, cTnT

NCBI Gene: 7139 ENSG00000118194 OMIM: 191045

The cardiac troponin T protein is the tropomyosin-binding subunit of the troponin complex that confers calcium-sensitivity to cardiac muscle contraction. Mutations cause autosomal dominant cardiomyopathies including hypertrophic, dilated, restrictive, and left ventricular noncompaction phenotypes. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.638), and comprehensive clinical management guidelines are available through GeneReviews.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismADLOEUF 0.644 OMIM phenotypes

Clinical Summary— TNNT2

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Gene-Disease Validity (ClinGen)

arrhythmogenic right ventricular cardiomyopathy · ADNo Known Disease Relationship

No known disease relationship

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

66 unique Pathogenic / Likely Pathogenic· 511 VUS of 1150 total submissions

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Clinical Trials

8 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — TNNT2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.002

Z-score 2.92

OE 0.37 (0.22–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.19Z-score

OE missense 0.74 (0.64–0.86)

121 obs / 163.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.22–0.64)

0≤0.351.4

Missense OE?0.74 (0.64–0.86)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 9 / 24.6Missense obs/exp: 121 / 163.9Syn Z: 0.06

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTNNT2-related hypertrophic cardiomyopathyOTHERAD

definitiveTNNT2-related dilated cardiomyopathyOTHERAD

This gene — mechanism propensity

0.76top 25%

GOF

0.4283th %ile

LOF

0.3066th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNExpression and functional assessment of a truncated cardiac troponin T that causes hypertrophic cardiomyopathy. Evidence for a dominant negative action1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 8958207 ↗

ClinVar Variant Classifications

1150 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic52

VUS511

Likely Benign388

Benign63

Conflicting113

Pathogenic

Likely Pathogenic

511

VUS

388

Likely Benign

Benign

113

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	13	0	0	14
Likely Pathogenic	10	42	0	0	52
VUS	64	365	79	3	511
Likely Benign	0	2	233	153	388
Benign	0	1	62	0	63
Conflicting	—				113
Total	75	423	374	156	1,141

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap TNNT2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

TNNT2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

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GeneReview available — TNNT2

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Fabry Disease

Biomarkers and Cardiac Imaging Diagnostic Assay for Monitoring Patients With Fabry Disease

RECRUITING

NCT05698901Mackay Memorial HospitalStarted 2023-09-19

Agalsidase beta

Multiple MyelomaAL Amyloidosis

A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL).

RECRUITING

NCT07638683Phase PHASE2Shanghai Zhongshan HospitalStarted 2026-05-22

Teclistamab

Systemic AmyloidosisATTR AmyloidosisAL Amyloidosis

Hungarian National Systemic Amyloidosis Registry

RECRUITING

NCT07689331Semmelweis UniversityStarted 2026-03-08

Systemic Sclerosis (SSc)

Tissue Modeling in Systemic Sclerosis Using Induced Pluripotent Stem Cells (iPSCs)

NOT YET RECRUITING

NCT07650565Phase NAUniversity Hospital, MontpellierStarted 2026-09

Blood Sample Collection