ClinVar

Description

This variant has been observed in individual(s) with multiple osteochondromatosis (PMID: 29529714). ClinVar contains an entry for this variant (Variation ID: 265126). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 268 of the EXT1 protein (p.Gly268Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. 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 EXT1 protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.p.Gly268 amino acid residue in EXT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19810120, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.