Here we report the identification of a novel SCN5A mutation leading to a so far unique combination of SCN5A-related cardiac disorders: bundle-branch block and long QT syndrome in the same individuals. In the ECG of the patients, lidocaine markedly shortened prolonged QT intervals and eliminated intermittent bundle-branch block. Genetic analysis revealed an exchange of a highly conserved threonine for a lysine at position 1620 in the cardiac sodium channel of the patients (Nav1.5). Electrophysiological measurements in Xenopus oocytes demonstrated that the T1620K mutation remarkably altered the properties of heterologously expressed Nav1.5 channels. In particular, the voltage-dependence of the current decay time constants was largely lost. We also found a hyperpolarized shift of steady-state activation, a decreased channel availability at the resting membrane potential, a slight increase of the persistent sodium current fraction, and an accelerated recovery from inactivation. We conclude that lysine at position 1620 leads to both loss-of-function and gain-of-function properties in Nav1.5, which may consequently cause in the same individuals impaired impulse propagation in the conduction system and prolonged QTc intervals, respectively.