Research on the distribution ratio of variants and the proportion of variant types in different conditions of SCN1A Seizure Disorders using ClinVar

Abstract The aim of this study was to clarify the distribution of SCN1A variants in each condition of SCN1A seizure disorders and the proportion of the SCN1A variant types in different conditions of SCN1A seizure disorders.This study consisted of querying SCN1A variants in ClinVar, reclassificating ClinVar P/LP SCN1A missense variants provided by a singgle submitter, validating conditions of SCN1A Seisure Disorders by reclassification of P/LP variants and screening variant types of conditions of SCN1A Seisure Disorders by validation.The result showed that most of the P/LP SCN1A missense variants provided by a single submitter in ClinVar remained at the P/LP level (247/383), and a few variants were converted from P/LP to VUS (136/383). The condition "Early infantile epileptic encephalopathy with suppression bursts" shown in ClinVar was actually all other conditons, such as Dravet syndrome/Severe myoclonic epilepsy of infancy(DS/SMEI)(69/89) and Generalized epilepsy with febrile seizures plus/Borderline severe myoclonic epilepsy of infancy(GEFS+/SMEB) (3/89). Both in missense and trunction, DS/SMEI-related SCN1A variants had the highest proportion (291/371, 78.4%),and there were still quite a few some SCN1A variants are associated with other conditions such as GEFS+, FMH, DEE, Lennox-Gastaut Syndrome and Intractable childhood epilepsy with generlaized tonic-clonic seizures (80/371, 21.6%).This provided data support for clinicians to grasp the severity of epilepsy caused by these SCN1A variants.