Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Foundation for Research in Genetics and Endocrinology, |
RCV000850231 | SCV000965690 | likely pathogenic | Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B | 2019-06-21 | criteria provided, single submitter | clinical testing | A heterozygous variant c.121G>A (p.Gly41Arg) in exon-1 has been observed in the TYR gene. The proband, born of a non-consanguineous marriage, was suspected to be affected with albinism. The patient in our clinical analysis was observed with the said variant in an autosomal recessive mode of inheritance. The variant has not been reported in the 1000 genomes database and has a minor allele frequency of 0.0008% and 0.007% in the ExAC databases. The in silico predictions of the variant are probably damaging by PolyPhen-2 (HumDiv), SIFT, LRT and MutationTaster2. In summary, the said variant meets our criteria to be classified as likely pathogenic based on the mode of inheritance, in silico prediction and allele frequency in population databases. |
| Labcorp Genetics |
RCV001858466 | SCV002225012 | likely pathogenic | not provided | 2024-04-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 41 of the TYR protein (p.Gly41Arg). This variant is present in population databases (rs369291837, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of oculocutaneous albinism and/or oculocutaneous albinism (PMID: 13680365, 19865097; Invitae). 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: 689488). 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%. Experimental studies have shown that this missense change affects TYR function (PMID: 27537549). 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. |
| Fulgent Genetics, |
RCV005004459 | SCV005631904 | likely pathogenic | Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN | 2024-03-25 | criteria provided, single submitter | clinical testing |