This variant is not present in control populations, is reported in several inherited erythromelalgia pedigrees and causes gain of function through a hyperpolarizing shift in the voltage dependence of activation.10,34 A pathogenic variant in SPTLC1 p.Cys133Trp was identified in a participant diagnosed with a painful sensorimotor neuropathy and is the commonest pathogenic SPTLC1 mutation causing hereditary sensory neuropathy type-1 identified in UK patients.35 This evidence concerns the gene SPTLC1 and erythromelalgia.