ClinVar

Description

This variant has not been reported in the literature in individuals affected with TYR-related conditions. 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.Ile198 amino acid residue in TYR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24934919). 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 TYR protein function. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, a(n) neutral and non-polar amino acid, with serine, a(n) neutral and polar amino acid, at codon 198 of the TYR protein (p.Ile198Ser).