Our analyses and the recently published UK Biobank analyses (17) discovered a second low-frequency non-synonymous SNV at CCDC141 (rs10497529, c. 442C > T, P. Ala141Val). CCDC141 (also known as CAMDI) encodes the coiled-coil domain containing 141 protein and interacts with DISC1 (disrupted in schizophrenia 1) and MYL2 (phosphorylatable myosin light chain). CCDC141 is highly expressed in heart muscle (30). Knockdown of CCDC141 in neurons leads to abnormal cortical neuronal migration, but there are otherwise limited functional studies of CCDC141 (30). The CCDC141 locus includes TTN (titin), which encodes a major structural protein in striated muscle. TTN mutations are associated with a range of hereditary myopathies (31). Prior work (12) using RNA interference in Drosophila melanogaster has shown that knockdown of TTN leads to significant changes in resting HR and HR post tachypacing, supporting TTN is a causal candidate gene at this locus. The new data described here implicate CCDC141 as a second candidate gene at this locus for functional follow-up.
