Table 4:
Field test of novel SNPs discovered in sequencing
| Classification |
Score |
Prediction confidence |
||||
|---|---|---|---|---|---|---|
| G290A | G298S | G290A | G298S | G290A | G298S | |
| SIFT | Affects protein function | Tolerated | 0.03 | 0.41 | Low | Good |
| PolyPhen | Benign | Benign | 1.016 | 0.038 | – | – |
| SNAP | Neutral | Neutral | – | – | 53% | 89% |
| Panther | – | – | – | – | – | – |
| nsSNP analyzer | – | – | – | – | – | – |
| PhD-SNP | Neutral | Disease | – | – | 4 | 0 |
| Auto-mute | – | – | – | – | – | – |
| FAST-SNP | – | – | – | – | – | – |
The TARDBP SNPs 869G->C (amino acid change G290A) and 892G->A (amino acid change G298S) were found to be statistically associated with disease in a case/control study of familial ALS with FTLD and putatively linked to loss and/or gain of protein function. Both SNPs were submitted to eight “Methods Servers” (Table 2A) for SNP function prediction to evaluate required user skills and agreement with associations from the case/control study. Three of the webservers were unable to classify these SNPs for technical reasons (detail in Supplementary Tables 2). FAST-SNP does not classify novel SNPs with respect to overall impact on disease risk, but it predicted that a TFBS might be affected by both of these SNPs. ‘–’ = not provided.