Table 3.
In vitro sensibility of SCN4A mutants to sodium channel blockers
| Mutation | Ref | Drug | Sensitivity* | Likely main mechanism / comments | |
| p.Val445Met | c.1333G>A | [101] | MEX | increased | increased inactivated state affinity |
| p.Ser804Phe | c.2411C>T | [101] | MEX | unchanged | |
| p.Ala1156Thr | c.3466G>A | [102] | MEX | unchanged | hyperPP phenotype |
| p.Pro1158Leu | c.3473C>T | [61] | MEX | reduced | Probably due to gating defect |
| p.Val1293Ile | c.3877G>A | [65, 101] | MEX | unchanged | |
| p.Asn1297Ser | c.3890A>G | [65] | MEX | reduced | Probably due to gating defect |
| FLE | unchanged | ||||
| p.Asn1297Lys | c.3891C>A | [65] | MEX | reduced | Probably due to gating defect |
| FLE | unchanged | ||||
| p.Phe1298Cys | c.3893T>G | [65] | MEX | reduced | Probably due to gating defect |
| FLE | unchanged | ||||
| p.Gly1306Glu | c.3917G>A | [102, 111] | MEX | reduced | Probably due to gating defect |
| [103] | FLE | unchanged | |||
| [105] | PIL | reduced | Probably due to gating defect | ||
| p.Ile1310Asn | c.3929T>A | [65] | MEX | reduced | Probably due to gating defect |
| FLE | increased | nd | |||
| p.Thr1313Met | c.3938C>T | [100] | LID | reduced | Right-shifted inactivation voltage dependence; reduced inactivated state affinity |
| [65] | MEX | reduced | Probably due to gating defect | ||
| FLE | increased | nd | |||
| PRO | unchanged | ||||
| p.Met1360Val | nd | [112] | MEX | unchanged | |
| p.Arg1448Cys | c.4342G>A | [100] | LID | increased | Probably due to gating defect |
| [102] | MEX | increased | Probably due to gating defect | ||
| [103] | FLE | increased | Probably due to gating defect | ||
| [105] | PIL | increased | Probably due to gating defect | ||
| [37] | RAN | increased | Probably due to gating defect | ||
| p.Arg1448His | c.4343G>A | [112] | MEX | increased | Probably due to gating defect |
| [37] | RAN | unchanged | |||
| p.Arg1448Pro | nd | [37] | RAN | increased | Probably due to gating defect |
| p.Phe1473Ser | nd | [111] | MEX | reduced | Probably due to gating defect |
| p.Met1476Ile | c.4428G>A | [113] | MEX | reduced | slower onset of mexiletine block and/or faster recovery from mexiletine block |
| p.Val1589Met | c.4765G>A | [101] | MEX | reduced | Reduced inactivated state affinity |
| p.Met1592Val | c.4774A>G | [101] | MEX | reduced | Reduced inactivated state affinity |
*compared to wild-type. FLE: flecainide; LID: lidocaine; MEX: mexiletine; nd: not defined; PIL: pilsicainide; PRO: propafenone; RAN: ranolazine.