Clinical Domain Working Groups

This expert panel will focus on curation of variants in the voltage-gated sodium channels, including alpha subunits SCN1A, SCN2A, SCN3A, and SCN8A, and their interacting beta subunit, SCN1B. Pathogenic variants in these genes are associated with a spectrum of epilepsy and related neurodevelopmental disorders. The panel has selected the aforementioned genes, in particular, as 1) these genes represent the more commonly identified monogenetic causes of epilepsy and thus present significant morbidity and mortality, and 2) recent progress in epilepsy genetics research has provided insight into therapeutic interventions for sodium channelopathies, providing opportunities for clinical trials for patients with these disorders.

Given the phenotypic and functional overlap of SCN1A, SCN2A, SCN3A, SCN8A, and SCN1B, in addition to the evolutionary conservation of these genes, it is suitable for this panel to curate these genes concurrently. We have assembled a diverse group of sodium channel gene experts from clinic, academia, and industry who specialize in neurology, epilepsy, genetics, laboratory genetics, animal models, channel electrophysiology and computational genetics to assume this task.  

Future considerations may include the SCN8A modifier, FGF12.