Table 1.
Relationship between the predictions derived from SIFT and Polyphen and the structural features calculated for the selected subset of variants. Unfavourable structural properties of the mutations are highlighted in bold and underlined, and partially unfavourable properties are highlighted in bold. The remaining properties were neutral. The first column contains the mutation; the second column contains the gene name; the third column contains the PDB identifier of the structure template; the fourth column lists the SIFT scores; the fifth column lists the Polyphen scores; the sixth column contains the prediction according to the SIFT and Polyphen scores as: ND: non-damaging and D: deleterious; the seventh column contains the polarity change in a hydrophobicity scale (see Materials and Methods); the eighth column contains the change in the protein charge, based on changes in the charge of the changed residue (see Materials and Methods); the ninth column lists the SNAP prediction, N: neutral and NN: non-neutral, with the accuracy in brackets; the tenth column contains the SMD prediction N: neutral, S: stabilizing, SS: slightly stabilizing, D: destabilizing, SD: slightly destabilizing and HD: highly stabilizing and causing protein malfunction; the eleventh column contains the SMD pseudo ΔΔG; and the twelfth column lists the change in percentage of solvent accessibility, coded as A: accessible, PA: partly accessible and B: buried
| SMD | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation | Gene | PDB ID | SIFT | PolyPhen | Prediction | Polarity | Charge | SNAP | PRED | ΔΔG | % Solvent accessibility | Secondary structure |
| T503A | SPG7 | 2QZ4_A | 0.37 | 0.001 | ND | 1/1 | 0/0 | N (53%) | N | 0.39 | 63.8 A/55.9 PA | h-bonded turn |
| R171Q | NFRKB | 3u21_A | 0.36 | 0.2249 | ND | 2/2 | +/0 | NN (58%) | N | 0.23 | 101.5 A/111.1 A | Bend |
| K267R | CA4 | 1ZNC_A | NA | 0.314 | ND | 2/2 | +/+ | N (92%) | S | 1.2 | 26.8 PA/33.8 PA | Loop or irregular |
| A7S | PDIA3 | 3F8U_A | 0.1 | 0 | ND | 1/1 | 0/0 | N (92%) | SD | −0.56 | 110.5 A/103.6 A | Loop or irregular |
| K215R | RBBP4 | 2XU7_A | 0.28 | 0 | ND | 2/2 | +/+ | N (85%) | SD | 0.92 | 41.4 PA/57.3 PA | Extended strand |
| L56M | RET | 2X2U_A | 0.46 | 0.003 | ND | 0/0 | 0/0 | N (89%) | SD | −0.69 | 3.6 B/4 B | Extended strand |
| R48K | LXN | 2BO9_D | 0.95 | 0 | ND | 2/2 | +/+ | N (92%) | SD | −0.64 | 53.7 PA/66.5 PA | Loop or irregular |
| P459L | BACE2 | 3ZKM_A | 0.62 | 0.397 | ND | 1/0 | 0/0 | N (69%) | SS | 0.81 | 33.8 PA/48 PA | Loop or irregular |
| Y623C | SF3B1 | 2FHO_A | 0 | 0.999 | D | 0/0 | 0/0 | NN (68%) | HD | 2.21 | 33.6 PA/45.5 PA | Alpha helix |
| T663I | SF3B1 | 2FHO_A | 0 | 0.998 | D | 1/0 | 0/0 | NN (58%) | HD | 2.58 | 6.8 B/8.6 B | Alpha helix |
| K700E | SF3B1 | 2FHO_A | 0 | 0.999 | D | 2/2 | +/− | NN (58%) | SS | 0.6 | 47 PA/38.2 PA | Alpha helix |
| E372G | PABPC1 | 4F02_A | 0 | 0.86 | D | 2/1 | −/0 | NN (82%) | HD | −2.8 | 72.2 A/58 PA | Alpha helix |
| R374C | PABPC1 | 4F02_A | 0 | 0.998 | D | 2/0 | +/0 | NN (78%) | N | −0.2 | 59.3 A/52 PA | Alpha helix |
| E114G | SDCBP | 1N99_A | 0 | 0.234 | D | 2/1 | −/0 | N (53%) | D | −1.79 | 62.8 A/72.4 A | Extended strand |
| R251G | RP2 | 3BH6_B | 0.05 | 0.998 | D | 2/1 | +/0 | NN (58%) | HD | −3.25 | 29.4 PA/66.9 PA | Alpha helix |
| T207M | AGT | 2WXW_A | NA | 0.991 | D | 1/0 | 0/0 | NN (82%) | S | 1.41 | 5.2 B/2.6 B | Extended strand |
| E322D | ATF4 | 1CI6_A | 0.01 | 0.998 | D | 2/2 | −/− | N (78%) | D | −1.75 | 77.4 PA/86.1 A | Alpha helix |
| T287M | GRB7 | 4K81_A | 0.03 | 0.895 | D | 1/0 | 0/0 | NN (70%) | S | 1.35 | 47.9 PA/55 PA | Loop or irregular |
| C79F | MAVS | 3J6C_A | 0 | 0.999 | D | 0/0 | 0/0 | NN (82%) | HD | −2.03 | 10.8 B/8.8 B | Loop or irregular |
| T124I | BAIAP2L1 | 2KXC_A | 0.05 | 0.042 | D | 1/0 | 0/0 | N (53%) | S | 1.94 | 44.9 PA/59.5 PA | Alpha helix |