ClinVar

Description

This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 70 of the VHL protein (p.Glu70Gly). This variant is present in population databases (rs786202857, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of von Hippel-Lindau syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 186316). 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 VHL protein function. This variant disrupts the p.Glu70 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9829912, 17661816, 19270817, 19408298, 25078357, 25562111, 25715769, 27439424; 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.