Fig. 4

Performance of weighted random forest model for splice-disrupting variants applied to external validation cohorts. The performance of the weighted model was assessed in two external validation cohorts. CHD validation cohort: a SpliceAI only AUC, b DNA variant features only AUC, c DNA variant features + myocardial RNA gene expression AUC, d SpliceAI + DNA variant features + myocardial RNA gene expression AUC. AUC was highest for model 4 in CHD cohort (n = 48). e The odds ratio for selecting variants confirmed to affect splicing was highest for model 4 in CHD cohort. Cardiomyopathy validation cohort: a SpliceAI only AUC, b DNA variant features only AUC, c DNA variant features + myocardial RNA gene expression AUC, d SpliceAI + DNA variant features + myocardial RNA gene expression AUC. AUC was highest for model 4 in cardiomyopathy cohort (n = 43). j The odds ratio for selecting variants confirmed to affect splicing was highest model 4 in cardiomyopathy cohort