ClinVar Miner

Submissions for variant NM_000104.4(CYP1B1):c.1310C>T (p.Pro437Leu)

gnomAD frequency: 0.00005  dbSNP: rs56175199
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001658811 SCV001873939 likely pathogenic not provided 2024-04-18 criteria provided, single submitter clinical testing In vivo and in vitro functional studies demonstrated that the presence of the P437L variant results in a dramatic decrease in enzymatic activity in comparison to wild-type (PMID: 27060699, 12807732); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25952714, 27268095, 15723004, 19204079, 9497261, 16735994, 12807732, 15475877, 22128238, 19528825, 20660114, 25978063, 34528698, 35170016, 27060699, 27535533)
Baylor Genetics RCV003470876 SCV004215486 pathogenic Anterior segment dysgenesis 6 2024-02-20 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001658811 SCV004235476 pathogenic not provided 2023-06-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003594146 SCV004292440 pathogenic Congenital glaucoma 2024-03-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 437 of the CYP1B1 protein (p.Pro437Leu). This variant is present in population databases (rs56175199, gnomAD 0.01%). This missense change has been observed in individual(s) with nonsyndromic primary congenital glaucoma (PMID: 9497261, 12036985, 19234632). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1254629). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CYP1B1 protein function. Experimental studies have shown that this missense change affects CYP1B1 function (PMID: 27060699). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005023212 SCV005663679 likely pathogenic Glaucoma 3A; Anterior segment dysgenesis 6 2024-05-29 criteria provided, single submitter clinical testing

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