Genotype-function-phenotype correlations for SCN1A variants identified by clinical genetic testing.

ABSTRACT:

Objective

Interpretation of clinical genetic testing, which identifies a potential genetic etiology in 25% of children with epilepsy, is limited by variants of uncertain significance. Understanding functional consequences of variants can help distinguish pathogenic from benign alleles. We combined automated patch clamp recording with neurophysiological simulations to discern genotype-function-phenotype correlations in a real-world cohort of children with SCN1A-associated epilepsy.

Methods

Clinical data were extracted for children with SCN1A variants identified by clinical genetic testing. Functional properties of non-truncating Na_V1.1 variant channels were determined using automated patch clamp recording. Functional data were incorporated into a parvalbumin-positi

SUBMITTER: Knox AT 

PROVIDER: S-EPMC11920720 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature