Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001969826 | SCV002219801 | pathogenic | not provided | 2024-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 97 of the TYR protein (p.Gly97Val). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with ocular albinism (PMID: 15381243, 27734839). 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: 1442280). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TYR protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects TYR function (PMID: 27537549). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001969826 | SCV002820517 | likely pathogenic | not provided | 2022-07-12 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect with absent enzyme activity (Mondal et al., 2016); Observed with a second variant in an individual with OCA in the literature, and testing of one parent suggests the variants are likely present on opposite alleles (in trans) (Goto et al., 2004); 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: 27537549, 15381243) |
Baylor Genetics | RCV003464274 | SCV004207575 | likely pathogenic | SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN | 2023-11-20 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005006284 | SCV005631912 | likely pathogenic | Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN | 2024-04-11 | criteria provided, single submitter | clinical testing |