ClinVar

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 345 of the SERPING1 protein (p.Gly345Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hereditary angioedema (PMID: 15971231, 16409206). It has also been observed to segregate with disease in related individuals. 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 SERPING1 protein function with a positive predictive value of 80%. This variant disrupts the p.Gly345 amino acid residue in SERPING1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.