ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg333 amino acid residue in SLC7A9. Other variant(s) that disrupt this residue have been observed in individuals with SLC7A9-related conditions (PMID: 16609684, 28646536), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects SLC7A9 function (PMID: 11157794). 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 SLC7A9 protein function. ClinVar contains an entry for this variant (Variation ID: 5787). This missense change has been observed in individuals with autosomal recessive cystinuria (PMID: 11157794, 16138908, 16225397, 25296721, 25964309, 28717662). This variant is present in population databases (rs121908484, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 333 of the SLC7A9 protein (p.Arg333Trp).