Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001958629 | SCV002235134 | pathogenic | not provided | 2023-02-05 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1455534). For these reasons, this variant has been classified as Pathogenic. 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. This missense change has been observed in individuals with oculocutaneous albinism (PMID: 18463683, 27734839). This variant is present in population databases (rs746581409, gnomAD 0.004%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 209 of the TYR protein (p.Pro209Leu). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004579584 | SCV005062106 | likely pathogenic | Oculocutaneous albinism | 2024-03-08 | criteria provided, single submitter | clinical testing | Variant summary: TYR c.626C>T (p.Pro209Leu) results in a non-conservative amino acid change located in the Tyrosinase copper-binding domain (IPR002227) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251364 control chromosomes. c.626C>T has been reported in the literature as a homozygous or compound heterozygous genotype in at-least three individuals affected with Oculocutaneous Albinism. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25216246, 18463683, 27734839). ClinVar contains an entry for this variant (Variation ID: 1455534). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Fulgent Genetics, |
RCV005002719 | SCV005631930 | likely pathogenic | Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN | 2024-03-07 | criteria provided, single submitter | clinical testing |