ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 360 of the AGXT protein (p.Arg360Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with primary hyperoxaluria type I (PMID: 21705122, 27935012, 30341509, 33721035). ClinVar contains an entry for this variant (Variation ID: 204147). 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 AGXT protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects AGXT function (PMID: 19479957, 30341509). This variant disrupts the p.Arg360 amino acid residue in AGXT. Other variant(s) that disrupt this residue have been observed in individuals with AGXT-related conditions (PMID: 25644115, 28893421), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.