ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp38 amino acid residue in TTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8579098, 15820680, 20209591; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TTR protein function. This variant is also known as p.D18E. This missense change has been observed in individual(s) with familial transthyretin amyloidosis (PMID: 7599630, 23713495, 26656838). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 38 of the TTR protein (p.Asp38Glu).