Submissions for variant NM_000104.4(CYP1B1):c.592G>A (p.Val198Ile)

gnomAD frequency: 0.00009  dbSNP: rs59472972

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001142193	SCV001302606	uncertain significance	Irido-corneo-trabecular dysgenesis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001142194	SCV001302607	uncertain significance	Glaucoma 3A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV001759901	SCV001985453	uncertain significance	not provided	2019-07-15	criteria provided, single submitter	clinical testing	Identified in the heterozygous state in a Japanese individual with primary congenital glaucoma and in a Chinese individual with primary open-angle glaucoma, and a second CYP1B1 variant was not reported in these individuals (Mashima et al., 2001; Chen et al., 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25527694, 11527932, 26550445)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002282462	SCV002571947	uncertain significance	not specified	2022-08-11	criteria provided, single submitter	clinical testing	Variant summary: CYP1B1 c.592G>A (p.Val198Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00028 in 187934 control chromosomes (gnomAD and publication data). This frequency is not significantly higher than expected for a pathogenic variant in CYP1B1 causing Primary Congenital Glaucoma (0.00028 vs 0.0043), allowing no conclusion about variant significance. c.592G>A has been reported in the literature in individuals affected with Primary Congenital Glaucoma (Mashima_2001, Chen_2008, Gong_2015, Liu_2020). These reports do not provide unequivocal conclusions about association of the variant with Primary Congenital Glaucoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV002491424	SCV002799766	uncertain significance	Glaucoma 3A; Glaucoma 3, primary infantile, B; Anterior segment dysgenesis 6	2022-04-04	criteria provided, single submitter	clinical testing
Invitae	RCV003758998	SCV004374903	benign	Congenital glaucoma	2024-01-09	criteria provided, single submitter	clinical testing