Fig. 6

Functional scores correlate with in vitro assays and clinical outcomes. A Correlation of function scores with peak current (normalized to WT) from patch clamp studies. Blue: currents obtained from literature review, pink: mean of currents from literature review and this study, yellow: currents measured in this study. B Variants generated by single SNVs (blue) are less likely to have low functional scores compared to all other variants (black; p = 2.0 × 10⁻², Wilcoxon Test). C Variants present in gnomAD (black) were more likely to have WT-like scores than variants absent from gnomAD (gray; p = 3.9. × 10⁻³, Wilcoxon test). Mean and confidence intervals are generated by re-sampling both distributions 100 times. D Functional scores by ClinVar classification. E Functional scores for presumed benign and presumed pathogenic variants. See Supplemental file 2 for the literature review dataset and Supplemental file 4 for an interactive worksheet with OddsPath calculations. F Receiver operator characteristic curves evaluating prediction of variant pathogenicity by functional and trafficking scores. Dots indicate the deleteriousness cutoffs used in this study (functional scores = 0.44, trafficking scores = 0.83). The area under the curve is listed at the bottom of the panel