Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays¹. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac (β-myosin heavy chain (cβMHQ^2,3) cardiac troponin T (cThT)^4,5, α-tropomyosin (αTM)^5'6, cardiac myosin binding protein C (cMBP-C)^7–9, ventricular myosin essential light chain (vMLC1)¹⁰ and ventricular myosin regulatory light chain (vMLC2)¹⁰ genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle¹¹, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnl), cardiac actin (cACT) and cardiac troponin C (cTnC)¹² in 184 unrelated patients with HCM and found mutations in the cTnl gene in several patients¹³. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnl is the seventh HCM gene.