Multiscale characterization of four Tropomyosin-1 variants of unknown significance

Mutations in proteins forming the contractile apparatus of cardiac muscle can alter muscle function, leading to a hypercontractile or a hypocontractile state of the heart. These mutational insults can also lead to secondary cardiac remodeling and disease states over time, resulting in either hypertrophic cardiomyopathy (HCM), affecting about 1 in 500 individuals, or dilated cardiomyopathy (DCM), affecting about 1 in 250 individuals. We are applying a broad range of techniques to follow the initial atomic-level insults to tissue-level remodeling and function in an effort to better understand mechanisms of disease.