Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002006905 | SCV002293819 | likely pathogenic | not provided | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 367 of the TYR protein (p.His367Tyr). This variant is present in population databases (rs776054795, gnomAD 0.002%). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 7955413, 18821858; Invitae). ClinVar contains an entry for this variant (Variation ID: 1506678). 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%. 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. |
Gene |
RCV002006905 | SCV002571642 | likely pathogenic | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing | Observed with a second TYR variant in a patient with oculocutaneous albinism in the published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Jackson et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17850513, 7955413, 18821858, 33458560, 28640309, 32830442) |
Baylor Genetics | RCV003471261 | SCV004207569 | likely pathogenic | SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN | 2024-02-16 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005008406 | SCV005631371 | likely pathogenic | Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN | 2024-06-23 | criteria provided, single submitter | clinical testing |