KCNQ2 and Encephalopathy: Although heterozygous missense variants clustered near the CaM-binding Helix A and B of the intracellular CT domain account for approximately 21% of cases of KCNQ2 encephalopathy (Millichap et al., 2016), studies to date have only begun to explain why very severe phenotypes result from some variants, while others cause benign familial neonatal epilepsy (Orhan et al., 2014; Soldovieri et al., 2016; Zhang et al., 2020).