FIGURE 5.

Structure-based metrics discriminate pathogenic from benign variants and provide mechanistic hypothesis of altered function. (A) The most informative structure-based metrics presented in previous figures were discretized and compared to commonly used genomics-based predictive algorithms (see the section “Materials and Methods”). Metrics from both perspectives effectively discriminate between pathogenic and benign variants. However, structure-based metrics provide mechanistic hypotheses for how the protein is altered by each variant. Additionally, they indicate more variable effects for VUSs than genomics-based predictors. (B) We visualized the similarity of variants to one another using MDS.