ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly117 amino acid residue in ASS1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12815590, 16124451, 27287393). 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 ASS1 protein function. ClinVar contains an entry for this variant (Variation ID: 813405). This missense change has been observed in individual(s) with citrullinemia type I (PMID: 12815590, 30285816). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 117 of the ASS1 protein (p.Gly117Asp).