ClinVar

Description

The p.E109Q pathogenic mutation (also known as c.325G>C), located in coding exon 3 of the TTR gene, results from a G to C substitution at nucleotide position 325. The glutamic acid at codon 109 is replaced by glutamine, an amino acid with highly similar properties. This alteration, which is also known as p.E89Q, was first described in an Italian family with hereditary transthyretin (TTR)-related amyloidosis (Almeida MR et al. Hum Mutat. 1992;1(3):211-5). This alteration is the most common TTR mutation in the Italian population and is associated with a mixed phenotype (Coelho T et al. Curr Med Res Opin. 2013;29(1):63-76; Rapezzi C. et al. Eur Heart J. 2013;34(7):520-8, Castaño A, et al. Heart Fail Rev 2015 Mar; 20(2):163-78). In addition, another mutation at the same position, p.E109K, has also been described in individuals with hereditary TTR-related amyloidosis (Barreiros AP, et al. Liver Transpl. 2010;16(3):314-23), Rapezzi C, et al. Eur. Heart J. 2013;34(7):520-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by BayesDel in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.