Recent exome sequencing studies identified filamin C ( ) as a candidate gene for hypertrophic cardiomyopathy (HCM). Our aim was to determine the rate of candidate variants in a large cohort of HCM patients who were also sequenced for the main sarcomere genes. A total of 448 HCM patients were next generation-sequenced (semiconductor chip technology) for the , , , , , , , , and genes. We also sequenced 450 healthy controls from the same population. Based on the reported population frequencies, bioinformatic criteria, and familial segregation, we identified 20 candidate variants (13 new; 1 nonsense; and 19 missense) in 22 patients. Compared with the patients, only 1 of the control's missense variants was nonreported ( =0.007; Fisher exact probability test). Based on the familial segregation and the reported functional studies, 6 of the candidate variants (in 7 patients) were finally classified as likely pathogenic, 10 as variants of uncertain significance, and 4 as likely benign. We provide a compelling evidence of the involvement of in the development of HCM. Most of the variants were associated with mild forms of HCM and a reduced penetrance, with few affected in the families to confirm the segregation. Our work, together with others who found variants among patients with dilated and restrictive cardiomyopathies, pointed to this gene as an important cause of structural cardiomyopathies.