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-ΔK184 in which >90% of cTnI (h-TG) is mutated have an increase in Ca2+-sensitivity and in passive force, and a slower rate of relaxation (Iorga et al., 2008). In patients the mutated protein amounts to typically <50%. Therefore, we investigated how myofibrillar function is affected in a mouse model in which only ∼10% of cTnI (l-TG) carries the mutation. In skinned fibers from the l-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 l-TG, p<0.01). In contrast, the increase in passive force and the slow down of the rate of relaxation was present not only in myofibrils from h-TG but also from l-TG mice. In line with these findings, tip catheter measurements showed an increase in end diastolic pressure in both h-TG and l-TG mice in vivo. Taken together our results demonstrate that even with a very low expression rate of the FHC-linked mutation, cTnI-ΔK184 signs of diastolic dysfunction both at the myofibrillar and organ level 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.