Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000085897 | SCV002236675 | pathogenic | not provided | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 371 of the TYR protein (p.Asn371Thr). This variant is present in population databases (rs61754387, gnomAD 0.002%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 29345414). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3798). 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.Asn371 amino acid residue in TYR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29345414). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000004002 | SCV000024168 | pathogenic | Tyrosinase-negative oculocutaneous albinism | 1992-07-15 | no assertion criteria provided | literature only | |
| Retina International | RCV000085897 | SCV000118040 | not provided | not provided | no assertion provided | not provided |