ClinVar Miner

Submissions for variant NM_000497.4(CYP11B1):c.124C>T (p.Pro42Ser)

gnomAD frequency: 0.00001  dbSNP: rs104894069
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001851529 SCV002128982 pathogenic not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 42 of the CYP11B1 protein (p.Pro42Ser). This variant is present in population databases (rs104894069, gnomAD 0.004%). This missense change has been observed in individual(s) with congenital adrenal hyperplasia (PMID: 9302260). 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: 1179). 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) performed at Invitae indicates that this missense variant is expected to disrupt CYP11B1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CYP11B1 function (PMID: 9302260, 26053152). This variant disrupts the p.Pro42 amino acid residue in CYP11B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26053152; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002476907 SCV002778462 likely pathogenic Deficiency of steroid 11-beta-monooxygenase; Glucocorticoid-remediable aldosteronism 2022-02-19 criteria provided, single submitter clinical testing
Baylor Genetics RCV000001238 SCV004215325 likely pathogenic Deficiency of steroid 11-beta-monooxygenase 2023-10-30 criteria provided, single submitter clinical testing
OMIM RCV000001238 SCV000021388 pathogenic Deficiency of steroid 11-beta-monooxygenase 1997-10-01 no assertion criteria provided literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029642 SCV000052294 not provided Congenital adrenal hyperplasia 2015-10-02 no assertion provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.