ClinVar

Description

This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 55 of the TTR protein (p.Lys55Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 16076613, 17028027, 19467548). This variant is also known as Lys35Asn. ClinVar contains an entry for this variant (Variation ID: 576496). 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 disrupts the p.Lys55 amino acid residue in TTR. Other variant(s) that disrupt this residue have been observed in individuals with TTR-related conditions (PMID: 21843040; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.