Interestingly, M145T in DIS1 in NaV1.1 (which corresponds to the last conserved residue in the S1 consensus motif) has been linked to familial febrile seizures and the activation curve of the mutant NaV1.1 has been reported to shift by 10 mV in a depolarizing direction [34]. This evidence concerns the gene SCN1A and Generalized epilepsy with febrile seizures-plus.