Figure 5

Arrhythmia-associated mutation and interspecific chemical severities correlate with the expected chemical severity of the reference codon in HERG and KCNQ1, but not with each other. a) Plot of AAM vs. interspecific chemical severities. No significant correlation is observed for either HERG (p = 0.20) or KCNQ1 (p = 0.10). b) Plots of AAM vs. expected chemical severities. A significant correlation is observed for both HERG (p < 0.0001) and KCNQ1 (p < 0.0001). c) Plots of interspecific vs. expected chemical severities (all sites). A significant correlation is observed for HERG (p = 0.0148) but not for KCNQ1 (p = 0.9918). For both proteins, the correlation (r) statistic, and the slopes of the regression, for interspecific vs. expected chemical severities are significantly smaller (p < 0.001) than those for AAM vs. expected chemical severities ('b', above). d) Plots of interspecific vs. expected chemical severities using only variable sites. A significant correlation is observed for both HERG (p < 0.0001) and KCNQ1 (p < 0.0001). The correlations and slopes of the linear regression are significantly larger (p < 0.001) than those using all sites ('c', above). For both proteins, the slopes of the linear regression are significantly smaller than those for AMM vs. expected chemical severities ('b', above) The correlation (r) is significantly smaller than that for AMM vs. expected chemical severities ('b', above) for HERG (p < 0.05) and not for KCNQ1 (p = 0.058). Significant differences in the average chemical severity were tested using the Mann-Whitney U test whereas the correlation differences between expected chemical severity and disease or interspecific severity were tested for significance using the z-score calculations.