CACNA1C and familial long QT syndrome: By whole-exome sequencing and bioinformatics/systemic biology, Boczek et al. further identified 4 novel mutations of CACNA1C in LQTS, including p.K834E, p.P857R, p.P857L, and p.R1906Q [84], 3 of which were located at the conserved proline, glutamic acid, serine and threonine rich (PEST) domain of CaVα1 II-III loop, this domain acts to proteolytic signaling through the cellular quality control system [85].