Therefore, it appears that more negative activation and window current are sufficient to induce GOF disease phenotypes, like in Cav2.1 for Familial hemiplegic Migraine Type I (FHM1; e.g., V714L, T501M, Hans et al., 1999; Carreño et al., 2013), in Cav1.3 for severe neurodevelopmental disorders (e.g., S652L, A749G, Ortner and Striessnig, 2020), in Cav1.2 for Timothy Syndrome (e.g., I1166T, Boczek et al., 2015) and in other Cavs (see below). Here, CACNA1C is linked to Timothy syndrome.