Dilated Cardiomyopathy (DCM) and Familial Hypertrophic Cardiomyopathy (FHC) are pathological heart conditions mainly associated with sarcomeric mutations that lead to contractile dysfunction. Despite the identification of several mutations associated with FHC and DCM, the role of these mutations in pathological cardiac-remodeling is still elusive. Therefore, we studied length-dependent contractile parameters of murine hearts expressing DCM-associated mutation (D230N in alpha-tropomyosin) and FHC-associated mutation (R92L in cTnT). Mechanical studies were carried out on detergent-skinned cardiac muscle fibers at sarcomere length (SL) 1.9 and 2.3 μm. Our preliminary results show that myofilament Ca2+ sensitivity and cooperativity are affected differently in both mutants, irrespective of SL. Ca2+ sensitivity was decreased in the D230N fibers, but increased in R92L fibers. Ca2+-activated maximal tension was unaltered in both examples. Cooperativity of myofilament activation was significantly decreased in R92L fibers and significantly increased in D230N fibers. Our results suggest that single amino acid substitution mutations in Tm (D230N) and TnT (R92L) cause diverse functional effects, which may correlate with varied pathological remodeling. Further mechano-dynamic studies are planned to determine if other aspects of myofilament activation may be involved in the evolution of complications associated with DCM and FHC.