Complex interactions in a novel SCN5A compound mutation associated with long QT and Brugada syndrome: Implications for Na+ channel blocking pharmacotherapy for de novo conduction disease.

While A647D mitigates the lethal LQT3 phenotype seen with P1332L, it also reduces mexilitine sensitivity and decreases INa density. These results explain our proband's mild repolarization abnormality and prominent conduction defect in the atria and ventricles, but also suggest that expression of P1332L with A647D yields a novel disease phenotype for which mexiletine pharmacotherapy is no longer suitable.