Sequence

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

Structure

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

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
• Gorevic PD, Prelli FC, Wright J, Pras M, and Frangione B. (1989). Systemic senile amyloidosis. Identification of a new prealbumin (transthyretin) variant in cardiac tissue: Immunologic and biochemical similarity to one form of familial amyloidotic polyneuropathy. J Clin Invest. 83:836-843
• Jacobson DR, Gorevic PD, and Buxbaum JN. (1990). A homozygous transthyretin variant associated with senile systemic amyloidosis: evidence for a late-onset disease of genetic etiology. Am J Hum Genet. 47:127-136
• Jacobson DR, Pastore R, Pool S, Malendowicz S, Kane I, Shivji A, Embury SH, Ballas SK and Buxbaum JN. (1996). Revised transthyretin Ile122 allele frequency in African-Americans. Hum Genet 98:236-238
• Saraiva MJM, Sherman W, Marboe C, Figueira A, Costa P, De Freitas AF, and Gawinowcz MA. (1990). Cardiac amyloidosis: Report of a patient heterozygous for the transthyretin isoleucine 122 variant. Scand J Immunol. 32:341-346
• Nichols WC, Liepnieks JJ, Snyder EL, and Benson MD. (1991). Senile cardiac amyloidosis associated with homozygosity for a transthyretin variant (ILE-122). J Lab Clin Med. 117:175-180
• Gillmore JD, Booth DR, Pepys MB, and Hawkins PN. (1999). Hereditary cardiac amyloidosis associated with the transthyretin Ile122 mutation in a white man. Heart (Br Card Soc Online). 82:e2
• Jiang X, Buxbaum JN, Kelly JW. The V122I cardiomyopathy variant of transthyretin increases the velocity of rate-limiting tetramer dissociation, resulting in accelerated amyloidosis. Proc Natl Acad Sci U S A. 2001;98: 14943–14948. doi:10.1073/pnas.261419998
• Buxbaum JN, Ruberg FL. Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans. Genet Med. 2017;19: 733–742. doi:10.1038/gim.2016.200
• Manral P, Reixach N. Amyloidogenic and non-amyloidogenic transthyretin variants interact differently with human cardiomyocytes: insights into early events of non-fibrillar tissue damage. Biosci Rep. 2015;35. doi:10.1042/BSR20140155

Studies on Therapeutic Strategy*

• 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

Available PDB Structures

• 1TTR