The known high-risk p.R190Q KCNQ1-variant needs a second hit for QTc prolongation.

The heterozygous missense p.R190Q KCNQ1 mutation represents one of the most frequent high-risk variants in long QT syndrome (LQTS). However, the presented case report and the data in literature led us to conclude that this heterozygous variant alone is associated with a low-penetrant clinical and electrocardiographical phenotype, while its co-inheritance with either the heterozygous p.E1053K SCN5A variant, some other LQTS-associated/modifying variant, or with some acquired QTc-inducing condition (like a specific leukaemia medication), may trigger QTc prolongation and thus a risk for arrhytmias.