What information does the TTN (Titin) gene provide about heart conditions?

From the Guidelines

The TTN gene provides crucial information about heart conditions by encoding titin, a protein that plays a vital role in heart muscle structure and function, and mutations in this gene are associated with various cardiac conditions, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. The TTN gene is now recognized as a significant contributor to heart disease, with mutations in this gene accounting for approximately 15-25% of familial cases of dilated cardiomyopathy [ 1 ]. These mutations typically lead to a truncated titin protein that compromises the structural integrity of heart muscle cells.

Clinical Implications of TTN Mutations

The clinical expression of TTN mutations varies widely, with some carriers developing severe heart failure while others remain asymptomatic, suggesting that additional genetic and environmental factors influence disease manifestation [ 1 ]. Understanding a patient's TTN status can guide personalized treatment approaches, family screening recommendations, and help predict disease progression in affected individuals.

Genetic Testing and TTN Variants

Genetic testing for TTN mutations can help identify at-risk individuals before symptoms develop, allowing for earlier monitoring and intervention [ 1 ]. The identification of TTN truncating variants (TTNtv) is crucial, as these variants are associated with an increased risk of cardiac conditions [ 1 ].

Disease Mechanisms and TTN

While the exact disease mechanisms of TTN mutations are still being elucidated, research suggests that TTN variants can lead to a range of cardiac conditions, including hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and restrictive cardiomyopathy [ 1 ]. Therefore, it is essential to consider TTN mutations in the diagnosis and management of heart conditions, and to prioritize genetic testing and family screening for individuals with a known family history of TTN-related cardiac conditions.

From the Research

Overview of the TTN Gene

• The TTN gene provides information about heart conditions, particularly cardiomyopathies, which are diseases of the heart muscle [ 2 ].
• The TTN gene encodes the protein titin, which is the largest protein in the human body and plays a crucial role in the structure and function of the heart muscle [ 3 ].

Association with Cardiomyopathies

• Mutations in the TTN gene have been associated with various forms of cardiomyopathy, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM) [ 2 , 4 ].
• TTN truncating variants are the most common cause of DCM, occurring in approximately 25% of familial cases and 18% of sporadic cases [ 5 ].

Clinical Implications

• The identification of TTN mutations can provide important information for the diagnosis and management of cardiomyopathies [ 2 ].
• Patients with TTN truncating variants are at increased risk of life-threatening cardiac arrhythmias and may benefit from implantable cardioverter-defibrillator (ICD) therapy [ 6 ].

Genetic Variation and Penetrance

• The TTN gene exhibits extensive genetic variation, with many different mutations and variants identified in patients with cardiomyopathy [ 2 ].
• The penetrance of TTN mutations can vary, with some mutations showing high penetrance and others showing lower penetrance [ 5 ].