Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255452 | SCV000321539 | pathogenic | not provided | 2022-03-03 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect, specifically, the variant causes reduced enzyme activity and decreased protein stability (Chavarria-Soley et al., 2008; Lopez-Garrido et al., 2010); Known as a Middle Eastern founder mutation (Li et al., 2011); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32153331, 33745036, 26982174, 27243976, 9463332, 9497261, 31024815, 21854771, 25091052, 19793111, 24591815, 19204079, 18470941, 19643970, 24210336, 21596299, 19234632, 12372064, 26164761, 24099281, 23363883, 25261878, 28448622, 16862072, 30127590, 30207287, 30270463, 31980526, 34426522, 31589614, 15621878, 15037581, 33170892) |
Fulgent Genetics, |
RCV000763083 | SCV000893609 | pathogenic | Glaucoma 3A; Glaucoma 3, primary infantile, B; Anterior segment dysgenesis 6 | 2022-03-24 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000008169 | SCV001162951 | pathogenic | Glaucoma 3A | criteria provided, single submitter | clinical testing | ||
Ce |
RCV000255452 | SCV001247370 | pathogenic | not provided | 2022-02-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001206715 | SCV001378037 | pathogenic | Congenital glaucoma | 2024-01-31 | 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 61 of the CYP1B1 protein (p.Gly61Glu). This variant is present in population databases (rs28936700, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individuals with primary congenital glaucoma (PMID: 9463332, 12372064, 19234632). It is commonly reported in individuals of Saudi and Moroccan ancestry (PMID: 9463332, 12372064, 19234632). This variant is also known as c.3987G>A. ClinVar contains an entry for this variant (Variation ID: 7730). 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 CYP1B1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CYP1B1 function (PMID: 18470941, 19793111, 27243976). For these reasons, this variant has been classified as Pathogenic. |
Institute of Medical Genetics and Applied Genomics, |
RCV000255452 | SCV001480127 | pathogenic | not provided | 2021-02-01 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001335112 | SCV001528169 | pathogenic | Anterior segment dysgenesis 6 | 2024-03-26 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000008169 | SCV001623487 | pathogenic | Glaucoma 3A | 2021-05-18 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000255452 | SCV002018104 | pathogenic | not provided | 2023-02-28 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV000008169 | SCV002557822 | pathogenic | Glaucoma 3A | 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 congenital, juvenile, or adult onset primary open anglet glaucoma 3A (MIM#231300) and anterior segment dysgenesis 6, multiple subtypes (MIM#617315). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0112 - The condition associated with this gene has incomplete penetrance (PMID: 26550445, 19744731). (I) 0115 - Variants in this gene are known to have variable expressivity. Individuals with the same variants have been reported with variable severity and age of onset (PMID: 19744731). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to glutamic acid. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (63 heterozygotes, 2 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated p450 domain (DECIPHER). (I) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. The p.(Gly61Arg) variant has been classified as pathogenic by a clinical laboratory in ClinVar. (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been observed in homozygous or compound heterozygous state in many individuals with primary congenital glaucoma, and has been described as hypomorphic due to its residual enzyme activity and reduced penentrance (ClinVar, DECIPHER, PMIDs: 19234632, 19744731). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. This variant has been shown to have 25% of wild type activity and significantly reduced protein expression using fluorimetric and western blot assays on transfected HEK-293T cells (PMID: 19234632). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Center for Genomic Medicine, |
RCV000008169 | SCV004847100 | pathogenic | Glaucoma 3A | 2024-03-17 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000008169 | SCV000028374 | pathogenic | Glaucoma 3A | 2002-10-01 | no assertion criteria provided | literature only | |
Department Of Genetics, |
RCV000008169 | SCV000891494 | pathogenic | Glaucoma 3A | 2024-06-12 | no assertion criteria provided | curation | |
Biochemical Molecular Genetic Laboratory, |
RCV000008169 | SCV001132972 | pathogenic | Glaucoma 3A | 2019-08-25 | no assertion criteria provided | clinical testing | |
OMIM | RCV001335112 | SCV001652917 | pathogenic | Anterior segment dysgenesis 6 | 2002-10-01 | no assertion criteria provided | literature only | |
Gene |
RCV000008169 | SCV002106340 | not provided | Glaucoma 3A | no assertion provided | literature only | ||
Coban- |
RCV003483427 | SCV004231748 | uncertain significance | Glaucoma 3A; Anterior segment dysgenesis 6 | no assertion criteria provided | clinical testing | The affected individual was severely delayed with no communication skills and died at a young age. Since the subject was deceased, we could not perform an ophthalmologic evaluation. |