Table 1.
Pathogenicity predictions for missense and splice site mutations based on in silico analyses.
| Amino acid change predictions | |||||||
|---|---|---|---|---|---|---|---|
| DNA change | Protein change | ExAC (MAF) | SIFT [0–1] | Provean* | Polyphen-2 [0–1] | Mutation Taster [0–1] | PhyloP [−14.1;6.4] |
| c.296 A > G | p.E99G | — | Deleterious (0.0) | Deleterious (−5.6) | Probably damaging (1.0) | Disease causing (1.0) | 4.08 |
| c.1311_1316del | p.L437_T438del | — | N/A | Deleterious (−11.5) | N/A | Disease causing (0.87) | N/A |
| c.1448 A > G | p.E483G | — | Deleterious (0.0) | Deleterious (−6.1) | Probably damaging (1.0) | Disease causing (1.0) | 4.56 |
| c.1700T > C | p.L567P | — | Deleterious (0.0) | Deleterious (−4.0) | Probably damaging (1.0) | Disease causing (1.0) | 1.58 |
| c.2108 G > A | p.G703D | — | Deleterious (0.01) | Neutral (−2.4) | Probably damaging (0.99) | Disease causing (1.0) | 4.08 |
| Splicing predictions | |||||||
| DNA change | Predicted effect | ExAC (MAF) | SSF [0–100] | MaxEnt [0–12] | NNSPLICE [0–1] | GeneSplicer [0–15] | HSF [0–100] |
| c.56-1 G > A | Broken acceptor site | 0.00092% | 92.71 → 0 | 10.34 → 0 | 0.98 → 0 | 12.64 → 0 | 93.45 → 0 |
| c.639 + 1delG | Broken donor site | — | 81.67 → 0 | 8.92 → 0 | 0.95 → 0 | 10.23 → 0 | 84.70 → 0 |
| c.783 G > A | Broken donor site | 0.34% | 76.64 → 0 | 7.85 → 3.07 (−60.9%) | N/A | 5.87 → 1.89 (−67.8%) | 85.75 → 75.17 (−12.3%) |
| c.2040 + 5 G > T | Broken donor site | — | 92.58 → 80.19 (−13.4%) | 10.03 → 5.41 (−46.1%) | 1.00 → 0.81 (−18.3%) | 10.35 → 6.32 (−39.0%) | 97.08 → 84.76 (−12.7%) |
ExAC, Exome Aggregation Consortium; MAF, minor allele frequency. *A score threshold of −2.5 was used. N/A, not applicable.