ClinVar Miner

Submissions for variant NM_000104.4(CYP1B1):c.1033C>T (p.Leu345Phe)

gnomAD frequency: 0.00012  dbSNP: rs66583685
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844442 SCV002103339 uncertain significance not specified 2023-12-07 criteria provided, single submitter clinical testing Variant summary: CYP1B1 c.1033C>T (p.Leu345Phe) results in a non-conservative amino acid change located in the I-helix of the heme-binding region (Vincent_2002) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 248598 control chromosomes, predominantly at a frequency of 0.0018 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in CYP1B1 causing Primary Congenital Glaucoma (0.00012 vs 0.0043), allowing no conclusion about variant significance. c.1033C>T has been reported in the literature in a heterozygous African-American individual affected with juvenile open-angle glaucoma (Vincent_2002). This report does 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. The following publication have been ascertained in the context of this evaluation (PMID: 11774072). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002482389 SCV002788736 uncertain significance Glaucoma 3A; Glaucoma 3, primary infantile, B; Anterior segment dysgenesis 6 2021-07-30 criteria provided, single submitter clinical testing
Invitae RCV003759080 SCV004385078 likely benign Congenital glaucoma 2024-01-17 criteria provided, single submitter clinical testing

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