Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Soonchunhyang University Bucheon Hospital, |
RCV000490426 | SCV000267279 | uncertain significance | Glaucoma 3A | 2016-03-18 | criteria provided, single submitter | reference population | |
| Eurofins Ntd Llc |
RCV000312523 | SCV000342292 | uncertain significance | not provided | 2016-05-17 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000490426 | SCV000914926 | uncertain significance | Glaucoma 3A | 2018-10-23 | criteria provided, single submitter | clinical testing | The CYP1B1 c.958G>T (p.Val320Leu) missense variant has been reported in at least four studies, in which it is found in a total of 13 individuals with primary congenital glaucoma, including in two in a compound heterozygous state, and in 11 in a heterozygous state in whom a second variant was not identified (Mashima et al. 2001; Kim et al. 2011; Su & Kee 2012; Do et al. 2016). The p.Val320Leu variant was also present in three additional individuals with primary open angle glaucoma, but the zygosity of the variant was unknown (Gong et al. 2015). The p.Val320Leu variant was present in four of 942 ethnically-matched control subjects and is reported at a frequency of 0.003615 in the East Asian population of the Genome Aggregation Database. Based on the evidence, the p. Val320Leu variant is classified as a variant of unknown significance but suspicious for pathogenicity for primary congenital glaucoma. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Fulgent Genetics, |
RCV002485372 | SCV002793162 | uncertain significance | Glaucoma 3A; Glaucoma 3, primary infantile, B; Anterior segment dysgenesis 6 | 2022-04-11 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003488467 | SCV004240895 | uncertain significance | not specified | 2023-12-12 | criteria provided, single submitter | clinical testing | Variant summary: CYP1B1 c.958G>T (p.Val320Leu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 248424 control chromosomes, predominantly at a frequency of 0.0038 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in CYP1B1 causing Primary Congenital Glaucoma (0.0038 vs 0.0043), allowing no conclusion about variant significance. c.958G>T has been reported in the literature, primarily in the heterozygous state, in individuals of East Asian ancestry affected with Primary Congenital Glaucoma (e.g. Mashima_2001, Kim_2011, Chen_2014, Do_2016), individuals with primary open-angle glaucoma (Gong_2015), and also in healthy controls (Kim_2011, Gong_2015). The variant was also found in the homozygous state in the unaffected mother of a heterozygous individual with Primary Congenital Glaucoma, providing supporting evidence for a benign role. 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: 24227805, 26550974, 25527694, 21850185, 11527932, 12598442, 22942166). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Invitae | RCV003758726 | SCV004454317 | benign | Congenital glaucoma | 2024-01-26 | criteria provided, single submitter | clinical testing |