TNNT2

Chr 1AD

troponin T2, cardiac type

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.644 OMIM phenotypes
Clinical SummaryTNNT2
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Gene-Disease Validity (ClinGen)
arrhythmogenic right ventricular cardiomyopathy · ADNo Known Disease Relationship

No known disease relationship

3 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.002
Z-score 2.92
OE 0.37 (0.220.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.19Z-score
OE missense 0.74 (0.640.86)
121 obs / 163.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.220.64)
00.351.4
Missense OE0.74 (0.640.86)
00.61.4
Synonymous OE0.99
01.21.6
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
DN
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 actionPMID:8958207

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TNNT2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Basis of Childhood Cardiomyopathy.
Bagnall RD et al.·Circ Genom Precis Med
2022
Hypertrophic Cardiomyopathy: Genes and Mechanisms.
Chen J et al.·Front Biosci (Landmark Ed)
2025Review
Dilated Cardiomyopathy Overview.
Adam MP et al.
2024Review
Top 5 results · since 2015Search PubMed ↗