Familial hypertrophic cardiomyopathy (HCM), due to point mutations in genes for 
sarcomere proteins such as myosin, occurs in 1/500 people and is the most common 
cause of sudden death in young individuals. Similar mutations in skeletal 
muscle, e.g., in the MYH7 gene for slow myosin found in both the cardiac 
ventricle and slow skeletal muscle, may also cause severe disease but the 
severity and the morphological changes are often different. In HCM, the modified 
protein function leads, over years to decades, to secondary remodeling with 
substantial morphological changes, such as hypertrophy, myofibrillar disarray, 
and extensive fibrosis associated with severe functional deterioration. Despite 
intense studies, it is unclear how the moderate mutation-induced changes in 
protein function cause the long-term effects. In hypertrophy of the heart due to 
pressure overload (e.g., hypertension), mechanical stress in the myocyte is 
believed to be major initiating stimulus for activation of relevant cell 
signaling cascades. Here it is considered how expression of mutated proteins, 
such as myosin or regulatory proteins, could have similar consequences through 
one or both of the following mechanisms: (1) contractile instabilities within 
each sarcomere (with more than one stable velocity for a given load), (2) 
different tension generating capacities of cells in series. These mechanisms 
would have the potential to cause increased tension and/or stretch of certain 
cells during parts of the cardiac cycle. Modeling studies are used to illustrate 
these ideas and experimental tests are proposed. The applicability of similar 
ideas to skeletal muscle is also postulated, and differences between heart and 
skeletal muscle are discussed.