Table 5 Guideline for evaluation of pathogenic potential of genes with de novo variants in epileptic encephalopathies

Possibly pathogenic with at least one of the following evidence:

1. Significantly high frequency or hotspot of variants in the patient group.

2. Other epilepsy-related phenotype with defined inheritance pattern.

3. Variants in the gene result in functional impairment that is related to epilepsy.

Pathogenic with at least one of the following specific evidence:

1. Variants of the gene are associated with characteristic phenotype.

2. Distinct correlation between genotype/funotype and phenotype.

3. Correlation between genetic impairment and phenotype severity, and it explains the severe phenotype.

4. Variant-specific model with corresponding phenotype, or defined mechanisms of epileptogenesis.