Table 1.
Early-infantile and later-onset phenotypes of recurrent Nav1.2 variants and their predicted functional impact.
| Variant (N) | Phenotype | DAPC prediction | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Un-affected (within early-infantile family) | Early-infantile benign | Early-infantile inter-mediate | Early-infantile severe | Later-onset (WS/un-classified infant-onset DEE) | Later-onset (LGS/un-classified childhood-onset DEE) | Later-onset (other epilepsy) | ID/ASD without epilepsy | ||
| Q1531K (8) | + | GoF | |||||||
| L1563V (6) | + | GoF | |||||||
| E1321K (5) | + | GoF | |||||||
| Y1589C (9) | + | + | NT (pr. GoF) | ||||||
| M252V (4) | + | + | NT (pr. GoF) | ||||||
| R223Q (17) | + | NT (pr. GoF) | |||||||
| L1330F (7) | + | NT (pr. GoF) | |||||||
| V208E (5) | + | NT (pr. GoF) | |||||||
| R36G (3) | + | NT (pr. GoF) | |||||||
| R1882G (2) | + | + | NT (pr. GoF) | ||||||
| D343G (2) | + | + | NT (pr. GoF) | ||||||
| V261L (2) | + | GoF | |||||||
| F1651C (2) | + | NT (pr. GoF) | |||||||
| R1319Q (16) | + | + | + | + | GoF | ||||
| A263V (11) | + | + | + | + | GoF | ||||
| Q383E (3) | + | + | + | GoF | |||||
| V1325I (3) | + | + | GoF | ||||||
| K908E (4) | + | + | NT (pr. GoF) | ||||||
| V261M (3) | + | + | NT (pr. GoF) | ||||||
| S987I (2) | + | + | NT (pr. GoF) | ||||||
| R1629H (4) | + | + | + | NT (pr. GoF) | |||||
| R1882Q (8) | + | + | GoF | ||||||
| M1338T (2) | + | + | NT (pr. GoF) | ||||||
| E999K (5) | + | GoF | |||||||
| R856Q (2) | + | GoF | |||||||
| V423L (2) | + | NT (pr. GoF) | |||||||
| S1336Y (2) | + | NT (pr. GoF) | |||||||
| R1626Q (2) | + | NT (pr. GoF) | |||||||
| G882E (2) | + | NT (pr. GoF) | |||||||
| N212D (2) | + | NT (pr. GoF) | |||||||
| E1211K (5) | + | LoF | |||||||
| D195G (2) | + | LoF | |||||||
| L1342P (5) | + | NT (pr. LoF) | |||||||
| R220Q (2) | + | NT (pr. LoF) | |||||||
| R853Q (14) | + | + | LoF | ||||||
| R1435* (2) | + | + | NT (pr. LoF) | ||||||
| K503fs* (2) | + | + | NT (pr. LoF) | ||||||
| R937C (4) | + | NT (pr. LoF) | |||||||
Phenotypic groups allocated according to age of seizure onset (< or ≥ age 3 months), and additional clinical features if seizure onset was at ≥ age 3 months (early-infantile if seizure onset between age 3 and 24 months and normal/near normal development prior to seizure onset and no epileptic spasms, later-onset for all others with seizure onset ≥ age 3 months). The correlation between variant, phenotypic group and biophysical impact was less robust if phenotypic groups were defined only by age of seizure onset. Plus sign patient(s) assigned to early-infantile or later-onset phenotypic groups.
Abbreviations: DEE developmental and epileptic encephalopathy, ID/ASD intellectual disability/autism spectrum disorder without seizures, DAPC dynamic action potential clamp, GoF gain-of-function, LoF loss-of-function, pr. presumed, NT not tested, N number of individuals with the recurrent variant, WS West syndrome, LGS Lennox–Gastaut Syndrome.