Truncated titin is incorporated into the sarcomere in human cardiac samples with dilated cardiomyopathy

Abstract

The most common genetic cause of dilated cardiomyopathy (DCM) is mutations in titin gene, TTN, with truncating variants (TTNtv). TTN encodes the giant protein titin, a large (3-4 MDa) and abundant protein that forms the third myofilament type of striated muscle. Titin spans half the sarcomere, from the Z-disk to the M-line. The underlying mechanisms by which titin mutations induce DCM are poorly understood.