Fig. 5

ESCOTT analysis of the P53 human protein. A ESCOTT and AlphaMissense matrices of mutational effects, with InterPro annotation of domains and interacting regions highlighting the significance of sensitive regions identified in the matrices. B AlfaFold structural model of the TP53 gene, including confidence scores plotted along the sequence and structural model. The inset legend explains the color scale. C Comparative analysis of TP53 “isoform- 8” (199aa; middle) and the corresponding subsequence of the primary isoform, “isoform- 1” (133–331; top). The difference matrix (bottom) highlights mutations with increased effect in isoform- 8: missense mutations from ClinVar predicted to be pathogenic in both isoforms (blue), mutations predicted to be pathogenic in both isoforms but not reported in ClinVar (green), and mutations predicted to be pathogenic only in isoform- 8 and not reported in ClinVar (cyan)