Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Foundation for Research in Genetics and Endocrinology, |
RCV000850232 | SCV000965691 | likely pathogenic | Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B | 2019-06-21 | criteria provided, single submitter | clinical testing | A heterozygous variant c.1037G>A (p.Gly346Glu) in exon-3 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. |
| Kariminejad - |
RCV001814229 | SCV001755304 | likely pathogenic | Abnormality of the skin | 2021-07-10 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV002272342 | SCV002557680 | pathogenic | Oculocutaneous albinism | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with TYR-related oculocutaneous albinism (MIM#203100, MIM#606952). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to glutamic acid. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (3 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (2 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated tyrosinase domain (DECIPHER). (I) 0703 - Other missense variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. These alternative changes (p.(Gly346Val) and p.(Gly346Arg)) have been reported as likely pathogenic or observed in a compound heterozygous individual with oculocutaneous albinism (OCA) (ClinVar, PMID: 16098056). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been previously reported as likely pathogenic, and observed in multiple homozygous and compound heterozygous individuals with OCA (ClinVar, PMID: 28266639, PMID: 8026428, PMID: 25216246, PMID: 15937636, PMID: 31077556). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Labcorp Genetics |
RCV002533774 | SCV003440585 | pathogenic | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 346 of the TYR protein (p.Gly346Glu). This variant is present in population databases (rs773970123, gnomAD 0.01%). This missense change has been observed in individuals with ocular albinism (PMID: 8026428, 25216246, 28266639, 31077556). ClinVar contains an entry for this variant (Variation ID: 617799). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the Gly346 amino acid residue in TYR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16098056, 32581362, 33800529). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003461012 | SCV004207623 | pathogenic | SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN | 2022-12-28 | criteria provided, single submitter | clinical testing | |
| University of Washington Center for Mendelian Genomics, |
RCV000755076 | SCV000882894 | likely pathogenic | Nonsyndromic Oculocutaneous Albinism | 2017-03-07 | no assertion criteria provided | research |