Fig. 7

Comparison of PRESCOTT, ESCOTT, EVE, ESM1b and AlphaMissense on human proteins in gnomAD and ACMG datasets. A Analysis of 1883 human proteins whose mutations collected in gnomAD v4.0.0 are labeled as pathogenic or benign in ClinVar. AUC curves for PRESCOTT, ESCOTT, EVE, ESM1b and AlphaMissense are superimposed. B PRESCOTT, ESCOTT, EVE, ESM1b and AlphaMissense distributions of scores for the 17,230 mutations of the 1883 human proteins. The plots split scores in two disjoint subsets, for mutations labeled as benign (blue) or pathogenic (red) by ClinVar. C. Global comparative analysis based on AUC scores for the 48 human proteins in the ACMG v3.1 dataset, for ESCOTT, PRESCOTT, EVE, ESM1b and AlphaMissense. Note that there is a structural model for 45 of the 48 proteins. The three remaining proteins, with a starred name in the figure, RYR2 = 5050 aa, RYR1 = 5122 aa and APOB = 4640 aa, have been evaluated with iGEMME. Note that all 48 proteins are represented by both benign and pathogenic mutations in ClinVar, and that both types of mutation are required to calculate the AUC and make the comparison. All proteins present at least 3 benign mutations in ClinVar. Compare with Additional file 1: Fig. S10 reporting the same analysis on 64 human proteins with at least 1 benign mutation described in ClinVar. D ESCOTT, PRESCOTT and AlphaMissense scores of 8 mutations are plot onto the MLH1 structure. These 8 mutations are labeled as benign/likely benign in ClinVar and are listed in Fig. 2G. Due to multiple mutations at position 618, only K618 T is plot. ESCOTT and PRESCOTT scores are reported in Fig. 2G. Color scale is as in Fig. 2. E ESCOTT, PRESCOTT and AlphaMissense scores of 14 mutations annotated as pathogenic/likely pathogenic in ClinVar are plotted onto the MYPC3 structure. ESCOTT and PRESCOTT displays show identical scores