With regards to the modulatory effects of LQTS‐associated CaM variants, we revealed that IKs current density was reduced across a range of membrane potentials at resting [Ca2+]cyt when modulated by all CaM variants, whereas only EF‐hand III mutants (D95V and N97I) significantly reduced IKs generated at high [Ca2+]cyt. Here, CALM1 is linked to familial long QT syndrome.