Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000085961 | SCV003300230 | pathogenic | not provided | 2022-07-15 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Arg217 amino acid residue in TYR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1642278, 10987646, 27734839). 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. ClinVar contains an entry for this variant (Variation ID: 99573). This missense change has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 18463683; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs63159160, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 217 of the TYR protein (p.Arg217Gly). For these reasons, this variant has been classified as Pathogenic. |
| Retina International | RCV000085961 | SCV000118104 | not provided | not provided | no assertion provided | not provided |