Targeted mutational analysis of ankyrin-B in 541 consecutive, unrelated patients referred for long QT syndrome genetic testing and 200 healthy subjects

Nonsynonymous ankyrin-B variants were detected in nearly 3% of unrelated LQTS patients and nearly 7% of healthy control subjects. Genotype-negative LQTS patients with a single ANK2 variant displayed nonexertional syncope, U waves, sinus bradycardia, and extracardiac findings. Whether the identification of previously reported functionally significant variants residing in 2% of apparently healthy subjects suggests proarrhythmic potential or potential misclassification warrants further scrutiny.