TRDN and Timothy syndrome: Variants in other cardiomyocyte ion channels or assembly proteins have been implicated in monogenic LQTS but, recently, the ability of variants in the beta subunit KCNE2 to cause disease in the absence of environmental or other genetic factors has been questioned.25 The contribution of genes involved in cellular calcium homeostasis is increasingly recognized: for example, CACNA1C underlies the multisystem Timothy syndrome, while the three calmodulin genes (CALM1, CALM2, CALM3) and triadin (TRDN) may cause highly malignant forms of LQTS.