TTRMDb
An amyloid disease database for transthyretin mutants
Sequence
| Analysis Tool |
Result |
| iMutant 3.0 | Destabilizing |
| STRUM | Destabilizing |
| iStable | Destabilizing |
| Provean | Deleterious |
| PredictSNP | Neutral |
| PhD-SNP | Deleterious |
| PolyPhen-2 | Deleterious |
| SIFT | Neutral |
| FATHMM | Damaging |
Structure
| Analysis Tool |
Result |
| mCSM | Destabilizing |
| SDM | Destabilizing |
| DUET | Destabilizing |
| DynaMut | Stabilizing |
| CUPSAT | Destabilizing |
| ENCoM | Destabilizing |
| FoldX (Protein Stability) | Reduces |
Aggregation
| Analysis Tool |
Result |
| TANGO (Aggregation Tendency) | No effect |
| WALTZ (Amyloid Propensity) | No effect |
| LIMBO (Chaperone Binding Tendency) | No effect |
Reported Articles
- Altland K, Benson MD, Costello CE, Ferlini A, Hazenberg BPC, Hund E, et al. Genetic microheterogeneity
of human transthyretin detected by IEF. ELECTROPHORESIS. 2007;28: 2053–2064.
doi:10.1002/elps.200600840
- Li S, Minnerath S, Ii K, Dyck PJ, and Sommer SS. (1991). Two-tiered DNA-based diagnosis of transthyretin
amyloidosis reveals two novel point mutations. Neurology. 41:893.
Studies on Therapeutic Strategy*
- Merlini G, Planté-Bordeneuve V, Judge DP, Schmidt H, Obici L, Perlini S, et al.
Effects of Tafamidis on Transthyretin Stabilization and Clinical Outcomes in
Patients with Non-Val30Met Transthyretin Amyloidosis. J Cardiovasc Transl Res.
2013;6: 1011–1020. doi:10.1007/s12265-013-9512-x
- Adams D, Gonzalez-Duarte A, O’Riordan WD, Yang C-C, Ueda M, Kristen AV, et
al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis.
N Engl J Med. 2018;379: 11–21. doi:10.1056/NEJMoa1716153
- Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, et
al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis.
N Engl J Med. 2018;379: 22–31. doi:10.1056/NEJMoa1716793
*includes studies on model organisms and commercially unavailable drugs