Gene TTN
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Also known as
Titin, Connectin, CMPD2, CMH9, LGMD2JOverview
TTN (Titin) encodes the largest known human protein, titin, which plays a crucial structural and regulatory role in striated muscle. Titin spans half of the muscle sarcomere, from the Z-disc to the M-line, and functions as a molecular spring that provides passive elasticity to muscle tissue. This giant protein is essential for sarcomere assembly, muscle contraction, and the maintenance of structural integrity in both cardiac and skeletal muscle.Mutations in TTN are a major cause of inherited cardiomyopathies, particularly dilated cardiomyopathy (DCM), accounting for approximately 25% of familial DCM cases. TTN variants can also cause hypertrophic cardiomyopathy, limb-girdle muscular dystrophy, and tibial muscular dystrophy. The clinical presentation varies widely depending on the specific mutation location and type, ranging from asymptomatic carriers to severe heart failure requiring transplantation.
Due to its enormous size (over 100,000 base pairs), TTN is highly susceptible to genetic variation, and distinguishing pathogenic variants from benign polymorphisms can be challenging. Understanding TTN carrier status is important for family planning, and early detection can enable monitoring and intervention to prevent or delay the onset of severe cardiac dysfunction.