ClinVar

Description

This variant has not been reported in the literature in individuals affected with TGM1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 358 of the TGM1 protein (p.Ser358Asn). 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 TGM1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ser358 amino acid residue in TGM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9261103, 27025581, 28403434). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.