Fig. 2

SAVs in ProNA-binding interfaces predicted strongly with effect. The crystal structure of the BRAF kinase domain in complex with MEK1 (PDB identifier 4MNF [36]) illustrated a typical example for residues predicted to bind with known and predicted effect. Residues in magenta-colored dots were predicted as ProNA-binding; residues in gray and black spheres marked effect variants (SAVs/missense SNVs/missense mutations) annotated by experiments (from either OMIM [21], HumVar [22], or PMD [23]); the gray/black shading was proportional to the SNAP2-score (prediction of effect), from white (SNAP2-score around 0, i.e. low likelihood of effect) to black (SNAP2-score > 90, i.e. high likelihood of effect predicted). For this representative example, 86% of the SAVs predicted strongly to have effect (SNAP2-score > 90) were predicted on binding residues, i.e. were covered by magenta-colored dots