ClinVar

Description

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. 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 has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 25455140, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 144106). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 247 of the TYR protein (p.Cys247Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine.