Point mutations in sarcomeric proteins have been identified as primary cause of fHCM, an autosomal dominant disease. Yet, the basic functional effects of these mutations are still unclear. Here we examined the functional effects of point mutations in the head domain of the cardiac myosin heavy chain (ß-MHC) in cardiac myocytes and slow skeletal muscle fibers from several individuals with fHCM. Quite heterogeneous functional changes e.g., of isometric force generation and calcium sensitivity were observed. In cardiac myocytes the effects of the mutation were the same as in soleus muscle from the same patient. In muscle fibers of two patients, however, no functional changes were detectible. To clarify the variability in the extent of functional effects we determined the ratio of mutated to wildtype myosin and ß-MHC-mRNA in the biopsies. In 7 out of 8 cases we found a significant deviation from the generally assumed 1:1 ratio between mutated and wildtype myosin and ß-MHC-mRNA. Interestingly, the samples where we could not identify functional effects contained the smallest amount (less than 25%) of mutated myosin. The results suggest that the severity of the disease not only depends on the location of the mutation in the myosin head domain, but also on the fraction of mutated myosin incorporated into the filaments.