Rivolta et al. (2001) identified 2 mutations at the same codon of the SCN5A gene: a tyr1795-to-cys mutation (Y1795C; ) in a patient with LQT3, and a Y1795H ( ) mutation in a patient with Brugada syndrome. Functional analysis revealed marked and opposing effects on channel gating consistent with activity associated with the cellular basis of each clinical disorder: Y1795H accelerated and Y1795C slowed the onset of activation; Y1795H, but not Y1795C, caused a marked negative shift in the voltage dependence of inactivation; and neither affected the kinetics of the recovery from inactivation. However, both mutations increased the expression of sustained Na(+) channel activity compared with wildtype channels, although this effect was most pronounced for the Y1795C mutation, and both promoted entrance into an intermediate or slowly developing inactivated state. Rivolta et al. (2001) concluded that these data confirmed the key role of the C-terminal tail of the cardiac Na(+) channel in the control of channel gating and provided further evidence of the close interrelationship between Brugada syndrome and LQT3 at the molecular level.