Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001756679 | SCV001986296 | uncertain significance | not provided | 2020-02-26 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Different missense changes at this residue and in nearby residues reported in the Human Gene Mutation database in association with oculocutaneous albinism, although evidence in support of pathogenicity is not available in some cases (Stenson et al., 2014); Identified in a patient with oculocutaneous albinism who also had two other variants in the TYR gene, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Opitz et al., 2004); This variant is associated with the following publications: (PMID: 10671066, 10094567, 19338054, 15146472, 23112997, 21749400, 25794181, 30868138) |
| Invitae | RCV001756679 | SCV003441026 | pathogenic | not provided | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 289 of the TYR protein (p.Cys289Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 10671066, 10987646). ClinVar contains an entry for this variant (Variation ID: 1303180). 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.Cys289 amino acid residue in TYR. Other variant(s) that disrupt this residue have been observed in individuals with TYR-related conditions (PMID: 13680365, 29345414), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |