Supplementary Material for: Whole-Exome Sequencing Identifies Two Novel TTN Mutations in Chinese Families with Dilated Cardiomyopathy

<b><i>Objectives:</i></b> Dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death. So far, only 127 mutations of <i>Titin</i><i>(TTN)</i> have been reported in patients with different phenotypes such as isolated cardiomyopathies, purely skeletal muscle phenotypes or complex overlapping disorders of muscles. <b><i>Methods:</i></b> We applied whole-exome sequencing (WES) to investigate cardiomyopathy patients and a cardiomyopathy-related gene-filtering strategy was used to analyze the disease-causing mutations. Sanger sequencing was applied to confirm the mutation cosegregation in the affected families. <b><i>Results:</i></b> A nonsense mutation (c.12325C&gt;T/p.R4109X) and a missense mutation (c.17755G&gt;C/p.G5919R) of <i>TTN</i> were identified in 2 Chinese DCM families, respectively. Both mutations were cosegregated in all affected members of both families. The nonsense mutation is predicted to result in a truncated TTN protein and the missense mutation leads to a substitution of glycine by arginine. Both variants may cause the structure changes of titin protein. <b><i>Conclusions:</i></b> We employed WES to detect the mutations of DCM patients and identified 2 novel mutations. Our study expands the spectrum of <i>TTN</i> mutations and offers accurate genetic testing information for DCM patients who are still clinically negative.