TNNI3 encodes troponin I3, the inhibitory subunit of the cardiac troponin complex that regulates thin filament dynamics during muscle contraction. It functions as a calcium-dependent regulatory protein that modulates the interaction between actin and myosin filaments, conferring calcium-sensitivity to cardiac muscle actomyosin ATPase activity 1. The protein binds to troponin C and troponin T within the sarcomeric troponin complex, enabling the heart to respond appropriately to changes in intracellular calcium concentration 2. Pathogenic variants in TNNI3 are associated with multiple inherited cardiomyopathies, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and restrictive cardiomyopathy. TNNI3 variants rank among the definitive HCM disease genes and are classified as moderate-evidence genes for DCM 31. In childhood cardiomyopathy cohorts, TNNI3 variants associate with more severe clinical outcomes compared to other sarcomeric genes 4. The penetrance of TNNI3 variants in HCM is approximately 60% in clinical families, with mean age at diagnosis around 38 years, though substantially lower (≈11%) in population-based studies 5. These findings underscore TNNI3's critical role in cardiac sarcomeric function and highlight its importance in genetic cardiomyopathy diagnosis.