Flowchart of this study. Patients of Brugada syndrome (BrS) cohort-I were assigned to groups of loss-of-function (LOF) SCN5A mutation carriers (N = 45), non-loss-of-function SCN5A variation carriers (N = 15), and SCN5A-mutation negative patients (SCN5A(−), N = 355) by in silico curation, PubMed search and functional evaluation using patch clamp. Numbers of unique variations (n) and patients (Pt) are shown where a duplication was identified. Brugada syndrome cohort-II consists of independent Brugada syndrome probands carrying no SCN5A rare variations.