Fig. 4

Venn diagrams summarizing the in silico prediction on 670 VUS from the GC-HBOC database. Variants classified as pathogenic by at least one program out of Align-GVGD, SIFT, MutationTaster2 and PolyPhen-2 are depicted in a), and variants classified as benign are shown in b). A total of 354 VUS were consistently classified as benign by all four tools under consideration, and 57 variants were consistently classified as pathogenic. In contrast, 57 variants were classified as benign exclusively by Align-GVGD, whereas 68 (30) were classified as pathogenic exclusively by PolyPhen-2 (SIFT). These inconsistent predictions point toward a noticeable amount of misclassifications by the corresponding tool