Table 1.
Forty-five in silico tools evaluated including components, training and test data sets.
| Tool name | Data output | Components of tool | Training data set(s) | Test (validation) data set(s) | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Categorical | Continuous | Evolutionary conservation | Protein features | Amino acid features | Nucleotide features | Clinical/population variation | Clinical classifications: ClinVar | Clinical classifications: HGMD | Clinical classifications: other | Nonclinical: human variation | Nonclinical: functional studies | Clinical classifications: ClinVar | Clinical classifications: HGMD | Clinical classifications: other | Nonclinical: human variation | Nonclinical: functional studies | ||
| Align-GVGD | ✓ | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||
| BayesDEL | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||
| CADD | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||
| CHASM | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||
| ClinPred | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||
| Condel | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||
| DANN | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||
| Eigen | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||
| FATHMM | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||
| FATHMM-MKL | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||
| fitCons | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||||
| GAVIN | ✓ | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||
| GenoCanyon | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||||
| GERP++ | ✗ | ✓ | ✓ | ✓ | ||||||||||||||
| Grantham score | ✗ | ✓ | ✓ | ✓ | ||||||||||||||
| LRT | ✗ | ✓ | ✓ | ✓ | ||||||||||||||
| M-CAP | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||
| Meta-SNP | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||||
| MetaLR | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||
| MetaSVM | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||||
| MLP | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||
| MSC | ✓ | ✗ | – | – | – | – | – | ✓ | ✓ | ✓ | ✓ | |||||||
| MutationAssessor | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||||
| MutationTaster2 | ✓ | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||
| MutPred | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||
| MVP | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||
| PANTHER | ✗ | ✓ | ✓ | ✓ | ✓ | |||||||||||||
| PhastCons | PhastCons100way | ✗ | ✓ | ✓ | ✓ | |||||||||||||
| PhastCons20way | ✗ | ✓ | ✓ | ✓ | ||||||||||||||
| PhD-SNPg | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||||
| PhyloP | PhyloP100 verebrate | ✗ | ✓ | ✓ | ✓ | |||||||||||||
| PhyloP20 mammalian | ✗ | ✓ | ✓ | ✓ | ||||||||||||||
| Pmut | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||
| PolyPhen-2 | HumDiv | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||
| HumVar | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||||
| PON-P2 | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||||
| PredictSNP | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||
| primateAI | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||
| PROVEAN | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||||
| REVEL | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||
| rfPred | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |||||||
| SIFT | ✗ | ✓ | ✓ | ✓ | ✓ | |||||||||||||
| SiPhy | ✗ | ✓ | ✓ | ✓ | ✓ | |||||||||||||
| SNAP2 | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||
| SNPs3D | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||||
| SuSPect (disease-susceptibility-based SAV phenotype prediction) | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||||||
| VEST3 | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||
| VEST4 | ✗ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||||
See Supplementary Table 1 for additional details on outputs, thresholds, variant types covered, and references.