Figure 6.

Correlation between the shift in voltage-dependent activation midpoint (V1/2) and phenotypes of pathogenic KCNQ2 variants in the VSD. Listed are 6 variants (at 5 codons) found recurrently, the shift observed under three informative and physiologically relevant subunit expression ratios (indicated schematically at top), and the associated phenotypes. The voltage shifts are taken from the publications listed. Remarkably, phenotypic severity appears correlated with the magnitude of the V1/2 shift, but even small shifts (R144W, R214W) can be pathogenic. These correlations are not interpreted as a necessarily complete pathogenic mechanism; and for LoF variants, additional disease pathomechanisms have been described (reviewed in 40).