N.S. : non statistically significant compared to WT ; N.A.: not available

COMMENTS TO IN VITRO DATA and CLINICAL PHENOTYPE
This mutation was identified in an infant who died suddenly at 9 weeks of age with documented TdP degenerating into ventricular fibrillation. The clinical diagnosis of LQTS was already made on day 2 after birth because of a prolonged QTc of 600 ms1/2 and recurrent TdP.
A1330P occurs in the DIIIS4-S5 region of SCN5A. The mutation causes a substitution from alanine to proline that may disrupt protein secondary structure and the alpha helix.

At variance with the "typical" LQT3 mutations the A1330P mutant did not exhibit a detectable persistent inward current. Instead a significnat shift in the voltage dependence of steady-state inactivation toward more positive values was observed. This shift in inactivation predicts an increased channel availability at the resting membrane potential of ventricular cells but more importantly, an increase in the amplitude of the window current (the maintained inward sodium current caused by an overlap in activation and inactivation).
Mutant channels exhibited a significantly slowed rate of current inactivation at potentials positive to -20 mV, whereas recovery from inactivation was accelerated. These results suggest that the A1330P mutation prolongs ventricular repolarization by an increase in sodium current during the plateau of the action potential caused