Table 2

Functional analysis of SCN8A mutations identified in heterozygous state in patients with intellectual disability (ID) with or without epileptic encephalopathy (EE)

Protein changeIDEECell assayEffect on functionRef.Channel domain
N1768D++NeuronalGOF, increased persistent current25In D4S6
T1716I++Neuronal GOF, hyperpolarizing shift in activation voltage28In D2S1
N984K++HEKGOF, hyperpolarizing shift in activation voltageThis articleNear D2S6
G1451S++HEKLOF at 37°CThis articlein D3S6
R223G++HEKPartial LOF; thermolabile.
Protein is unstable at 37°C, active at 30°C
32In D1S4
P1719Rfs*6+NoneLOF, protein truncation24In D4S5-S6
D58N+HEKWildtype activity; may be non-pathogenic in view of additional de novo mutationThis articleIn N-term 
  • Missense mutations were introduced into the mouse NaV1.6 cDNA and cells were transfected for electrophysiological assays. Only the deduced protein changes (one-letter code) are provided.

  • GOF, gain of function; LOF, loss of function.