Sequence

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

Structure

Analysis Tool	Result
mCSM	Destabilizing
SDM	Stabilizing
DUET	Stabilizing
DynaMut	Destabilizing
CUPSAT	Destabilizing
ENCoM	Destabilizing
FoldX (Protein Stability)	Slightly Reduces

Aggregation

Analysis Tool	Result
TANGO (Aggregation Tendency)	No effect
WALTZ (Amyloid Propensity)	No effect
LIMBO (Chaperone Binding Tendency)	No effect

Reported Articles

• Saeki Y, Ueno S, Takahashi N, Soga F, and Yanagihara T. (1992). A novel mutant (transthyretin Ile-50) related to amyloid polyneuropathy. FEBS Lett. 308:35.
• Nishi H, Kimura A, Harada H, Hayashi Y, Nakamura M, and Sasazuki T. (1992). Novel variant transthyretin gene (Ser50 to Ile) in familial cardiac amyloidosis. Biochem Biophys Res Commun. 187:460-466.
• Date Y, Nakazato M, Kangawa K, Shirieda K, Fujimoto T, and Matsukura S. (1997). Detection of three transthyretin gene mutation in familial amyloidotic polyneuropathy by analysis of DNA extracted form formalin-fixed and paraffin-embedded tissues. J Neurol Sci. 150:143-148.
• Mambule C, Ando Y, Nakamura M, Kusunose Y, Obayashi K, Tashima K, Ando E, Yamashita T, Terazaki H, Uchino M, and Ando M. (1999). Clinical Manifestations of Familial Amyloidotic Polyneuropathy (FAP) (ATTR Thr49Ile). The 4th Int’l Symp on FAP and Other TTR Related Disorders. Umeå Sweden, June 1999.
• Sakashita N, Ando Y, Obayashi K, Terazaki H, Yamashita T, Takei M, and Takahashi K. (1999). Familial amyloidotic polyneuropathy (Ser50Ile): The first autopsy case report. The 4th International Symposium on FAP and Other TTR Related Disorders. Umeå Sweden, June 1999.
• Sakashita N, Ando Y, Obayashi K, Terazaki H, Yamashita T, Takei M, Kinjo M, and Takahashi K. (1999). Familial amyloidotic polyneuropathy (Ser50Ile): The first autopsy case report. Virchows Arch. 436:345-350.

Studies on Therapeutic Strategy*

• Tojo K, Sekijima Y, Kelly JW, Ikeda S. Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis. Neuroscience Research. 2006;56: 441–449. doi:10.1016/j.neures.2006.08.014
• 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

*includes studies on model organisms and commercially unavailable drugs