Point mutations in genes coding for cardiac troponin-I (cTnI) were linked to familial hypertrophic cardiomyopathy (FHC). We have shown that cardiac myofibrils isolated from a transgenic mouse model carrying the FHC-linked mutation cTnI-DK184 in which >90% of cTnI (High-TG) is mutated have an increase in Ca²⁺-sensitivity and in passive force, and a slower relaxation rate constant (Iorga et al., 2008). Because in patients the mutated protein amounts to typically <50% we investigated how myofibrillar function is affected in a mouse model in which only ~10% of cTnI (Low-TG) carries the mutation. In skinned fibers from the Low-TG-mice, Ca²⁺-sensitivity was similar in WT and TG-mice at 110% of slack length. After pre-stretching the fibers to 125% of slack length, Ca²⁺-sensitivity in TG-fibers was higher compared to WT (pCa₅₀ 5.32 in WT and 5.49 in Low-TG, p<0.01). In contrast, the increase in passive force and the slow down of the relaxation rate constant was present not only in myofibrils from High-TG- but also from Low-TG-mice. In line with these findings, tip catheter measurements showed an increase in end diastolic pressure in both High-TG- and Low-TG-mice in vivo. Our results demonstrate that even with a low expression rate of the FHC-linked mutation cTnI-DK184, signs of diastolic dysfunction both at the myofibrillar and organ levels can be detected. The effects of the mutation on the systolic function in contrast appear to depend on the expression level of the mutant protein. This dose dependency may thus underlie at least in part the variable gene-phenotype relation.