Kd was significantly increased from 1.65 ± 0.08 μM (CaM-WT, n = 5) to 28.3 ± 0.9 μM (CaM-E140G, n = 5), indicating a ∼17-fold decrease in Ca2+-binding affinity for the LQTS-associated variant. Here, CALM1 is linked to familial long QT syndrome.