Titin, an important protein in the sarcomere, is the largest human protein. This study identified mutations in the titin gene that result in a truncated protein as important causes of dilated cardiomyopathy. Gene mutation is an important cause of cardiomyopathy. Mutations in eight sarcomere-protein genes cause hypertrophic cardiomyopathy, detected in 40 to 70% of patients. 1 , 2 Variations in more than 40 genes, most of which encode components of the sarcomere, the cytoskeleton, or the nuclear lamina, have been shown or posited to cause dilated cardiomyopathy. 3 , 4 Clinical evaluation identifies 30 to 50% of patients with dilated cardiomyopathy as having a relative who is affected or likely to be affected, 5 – 7 implicating a genetic cause. However, pathogenic mutations have been found in only 20 to 30% of patients. 8 TTN, the gene encoding titin, . . .