TNNI3
Chr 19ARADtroponin I3, cardiac type
Also known as: CMD1FF, CMD2A, CMH7, RCM1, TNNC1, cTnI
Cardiac troponin I is the inhibitory subunit of the troponin complex that regulates calcium-sensitive contraction in cardiac muscle by controlling actin-myosin interactions. Mutations cause multiple forms of cardiomyopathy including hypertrophic, restrictive, and dilated cardiomyopathy with both autosomal dominant and autosomal recessive inheritance patterns. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.69), and comprehensive clinical management guidelines are available through GeneReviews.
No known disease relationship
4 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TNNI3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Biomarkers and Cardiac Imaging Diagnostic Assay for Monitoring Patients With Fabry Disease
RECRUITINGMulti-center, Open-label, Single-ascending Dose Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM
RECRUITINGStudy of Safety, Tolerability and Efficacy of GB221 in Infants With Spinal Muscular Atrophy Type 1
RECRUITINGExternal Resources
Links to major genomics databases and tools