Sequence

Analysis Tool	Result
iMutant 3.0	Destabilizing
STRUM	Destabilizing
iStable	Destabilizing
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)	Slightly Reduces

Aggregation

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

Reported Articles

• Murakami T, Tachiban S, Endo Y, Kawai R, Hara M, Tanase S, and Ando M. (1994). Familial carpal tunnel syndrome due to amyloidogenic transthyretin His114 variant. Neurology. 44:315-318
• Mochizuki H, Kamakura K, Masaki T, Hirata A, Tokuda T, Yazaki M, Motoyoshi K, and Ikeda S. (2001). Nodular cutaneous amyloidosis and carpal tunnel syndrome due to the amyloidogenic transthyretin His 114 variant. Amyloid. 8(2):105-110

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

*includes studies on model organisms and commercially unavailable drugs

Available PDB Structures

• 3CXF