ClinVar Miner

Submissions for variant NM_000497.4(CYP11B1):c.896T>C (p.Leu299Pro)

gnomAD frequency: 0.00001  dbSNP: rs387907573
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000050224 SCV000799205 likely pathogenic Deficiency of steroid 11-beta-monooxygenase 2018-04-06 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000991870 SCV001143702 pathogenic not provided 2019-06-12 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/282818 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Damaging to protein function(s) relevant to disease mechanism. Very strong co-segregation with disease, and data include affected and unaffected individuals from multiple families.
GeneDx RCV000991870 SCV002558621 pathogenic not provided 2022-01-20 criteria provided, single submitter clinical testing Published functional studies demonstrate reduced CYP1B1 enzymatic activity (Krone N et al., 2005); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34426522, 26956189, 18663314, 15755848, 28228528, 29626607, 24022297)
Baylor Genetics RCV000050224 SCV004215348 pathogenic Deficiency of steroid 11-beta-monooxygenase 2023-08-06 criteria provided, single submitter clinical testing
Invitae RCV000991870 SCV004309161 pathogenic not provided 2023-07-03 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 299 of the CYP11B1 protein (p.Leu299Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of 11β-hydroxylase deficiency (PMID: 15755848, 18663314, 28228528, 33830237). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56832). 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 CYP11B1 protein function. Experimental studies have shown that this missense change affects CYP11B1 function (PMID: 15755848, 18663314). For these reasons, this variant has been classified as Pathogenic.
Pediatric Endocrinology Laboratory; Christian Albrechts University of Kiel RCV000050224 SCV000082803 not provided Deficiency of steroid 11-beta-monooxygenase no assertion provided not provided

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