ClinVar

Description

This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Glu81 amino acid residue in TTR. Other variant(s) that disrupt this residue have been observed in individuals with TTR-related conditions (PMID: 8352764, 28991715), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 572472). This variant is also known as p.Glu61Lys. This missense change has been observed in individual(s) with familial transthyretin amyloidosis (PMID: 17453626). This sequence change replaces glutamic acid with glycine at codon 81 of the TTR protein (p.Glu81Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine.