Location: A surrogate for personalized treatment of sodium channelopathies.

Voltage-gated sodium channels have been implicated in numerous inherited paroxysmal disorders of the nervous system, muscle, and heart. Our goal is to provide a framework that helps neurologists understand the clinical and treatment implications of sodium channel variants they encounter in clinical practice. This will be accomplished through our objectives of (1) recognizing the relationship between location of a missense sodium channel gene variant and its effect on channel function, and (2) categorizing clinical phenotype based on functional effect of a variant. The relationship between location, function, and treatment response is also discussed. These interactions can be illustrated by the sodium channelopathies seen in people with epilepsy but generalize beyond that disorder. Ann Neurol 2018;83:1-9.