Sequence

Analysis Tool	Result
iMutant 3.0	Stabilizing
STRUM	Destabilizing
iStable	Stabilizing
Provean	Deleterious
PredictSNP	Deleterious
PhD-SNP	Deleterious
PolyPhen-2	Deleterious
SIFT	Deleterious
FATHMM	Damaging

Structure

Analysis Tool	Result
mCSM	Destabilizing
SDM	Stabilizing
DUET	Destabilizing
DynaMut	Destabilizing
CUPSAT	Stabilizing
ENCoM	Destabilizing
FoldX (Protein Stability)	No effect

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
• Wallace MR, Dwulet FE, Williams EC, Conneally PM, Benson MD. Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis. J Clin Invest. 1988;81: 189–193. doi:10.1172/JCI113293

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
• Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013;369: 819–829. doi:10.1056/NEJMoa1208760
• 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