Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230403 | SCV003928950 | pathogenic | Oculocutaneous albinism | 2023-04-25 | criteria provided, single submitter | clinical testing | Variant summary: TYR c.1168C>G (p.His390Asp) 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 4e-06 in 251072 control chromosomes (gnomAD). c.1168C>G has been reported in the literature in multiple individuals affected with Oculocutaneous Albinism (e.g. Hutton_2008, Wei_2010, Wei_2011, Zhong_2019). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 18463683, 21458243, 19865097, 31077556). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000085906 | SCV004296120 | pathogenic | not provided | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 390 of the TYR protein (p.His390Asp). This variant is present in population databases (rs62645914, gnomAD 0.0009%). This missense change has been observed in individual(s) with ocular albinism (PMID: 9259202, 19865097, 31077556, 34838614). ClinVar contains an entry for this variant (Variation ID: 99539). 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%. For these reasons, this variant has been classified as Pathogenic. |
| Retina International | RCV000085906 | SCV000118049 | not provided | not provided | no assertion provided | not provided |