ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys89 amino acid residue in TYR. Other variant(s) that disrupt this residue have been observed in individuals with TYR-related conditions (PMID: 25216246), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 3781). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 1899321, 16517127, 27734839). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 89 of the TYR protein (p.Cys89Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine.