Table 1. Rules used by PolyPhen to predict effect of nsSNPs on protein function and structure.
| Rules (connected with logical AND) | Prediction | ||
|---|---|---|---|
| PSIC score difference Δ | Substitution site properties | Substitution type properties | |
| Arbitrary | Annotated as a functionala or bond formationb site | Arbitrary | Probably damaging |
| Not considered | In a region annotated or predicted as transmembrane | PHAT matrix difference resulting from substitution is negative | Possibly damaging |
| Δ ≤ 0.5 | Arbitrary | Arbitrary | Benign |
| Δ > 1.0 | Atoms are closer than 3.0 Å to atoms of a ligand or residue annotated as BINDING, ACT_SITE, LIPID, METAL | Arbitrary | Probably damaging |
| 0.5 < Δ ≤ 1.5 | Normed accessibility ACC ≤ 15% | Absolute change of accessible surface propensity is ≥0.75 or absolute change of side chain volume is ≥60 | Possibly damaging |
| Normed accessibility ACC ≤ 5% | Absolute change of accessible surface propensity is ≥1.0 or absolute change of side chain volume is ≥80 | Probably damaging | |
| 1.5<Δ ≤ 2.0 | Arbitrary | Arbitrary | Possibly damaging |
| Δ > 2.0 | Arbitrary | Arbitrary | Probably damaging |
One row corresponds to one rule, which may consist of several parts connected by logical AND. For a given substitution, all rules are tried one by one, resulting in prediction of functional effect: benign, possibly damaging or probably damaging. If no evidence for a damaging effect is seen, substitution is considered benign.
aBINDING, ACT_SITE, SITE, MOD_RES, LIPID, METAL, SE_CYS (SwissProt feature table terms).
bDISULFID, THIOLEST, THIOETH (SwissProt feature table terms).