Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000501190 | SCV000597802 | likely pathogenic | Tyrosinase-negative oculocutaneous albinism | 2017-03-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001857180 | SCV002185094 | pathogenic | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 212 of the TYR protein (p.Arg212Lys). This variant is present in population databases (rs377209424, gnomAD 0.004%). This missense change has been observed in individual(s) with ocular albinism (PMID: 13680365, 28976636). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 437182). 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 with a positive predictive value of 80%. This variant disrupts the p.Arg212 amino acid residue in TYR. Other variant(s) that disrupt this residue have been observed in individuals with TYR-related conditions (PMID: 19865097, 31077556, 31199599), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003464077 | SCV004207592 | pathogenic | SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN | 2023-07-18 | criteria provided, single submitter | clinical testing |