TTN Gene: Titin - Structure, Function, and Clinical Significance

The TTN gene encodes titin, a giant sarcomeric protein that spans half the sarcomere and is essential for muscle elasticity, structural integrity, and force transmission. Titin is the largest known human protein, with over 35,000 amino acids. It contains multiple immunoglobulin-like and fibronectin type III domains, as well as a kinase domain. TTN truncating variants are a major cause of dilated cardiomyopathy and are also associated with various skeletal muscle myopathies and muscular dystrophies.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Striated Muscle Contraction (Reactome: R-HSA-390522)

• Cardiac conduction (Reactome: R-HSA-5576891)

• Dilated cardiomyopathy (KEGG: hsa05414)

• Hypertrophic cardiomyopathy (KEGG: hsa05410)

Titin is the largest known human protein (3.8 MDa), composed of 34,350 amino acids. It functions as a molecular spring that controls sarcomere elasticity and provides structural stability. The protein contains multiple immunoglobulin-like and fibronectin type III domains, a serine/threonine kinase domain at the M-band, and binding sites for numerous sarcomeric proteins including myosin, actin, telethonin, and obscurin. Titin's elastic I-band region is responsible for passive tension in muscle, while the A-band region anchors thick filaments. Mutations in TTN are a leading cause of dilated cardiomyopathy and contribute to various skeletal muscle disorders.