In summary, further studies on possible interactions between sex and sequence variants in basic science models as well as heterogeneous LQTS samples are needed to elucidate underlying mechanisms as well as whether our finding is specific to these founder populations or generalizable to the LQT1/LQTS populations, especially as NOS1AP sequence variants are emerging as markers not only for QT prolongation but also clinical risk stratification for LQTS families [13, 14, 36]. This evidence concerns the gene KCNQ1 and familial long QT syndrome.