ClinVar

Description

This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 142 of the TYR protein (p.Lys142Met). This variant is present in population databases (rs754250982, gnomAD 0.02%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 18701257, 19865097, 22097729, 31077556). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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. Experimental studies have shown that this missense change affects TYR function (PMID: 27537549). For these reasons, this variant has been classified as Pathogenic.