ClinVar Miner

Submissions for variant NM_000497.4(CYP11B1):c.995G>A (p.Arg332Gln)

gnomAD frequency: 0.00002  dbSNP: rs149881706
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001382848 SCV001581795 pathogenic not provided 2023-12-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 332 of the CYP11B1 protein (p.Arg332Gln). This variant is present in population databases (rs149881706, gnomAD 0.01%). This missense change has been observed in individual(s) with adrenal hyperplasia (PMID: 24022297). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 56835). 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: 24022297). This variant disrupts the p.Arg332 amino acid residue in CYP11B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26476331). 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.
Baylor Genetics RCV000050227 SCV004215359 likely pathogenic Deficiency of steroid 11-beta-monooxygenase 2023-05-24 criteria provided, single submitter clinical testing
Pediatric Endocrinology Laboratory; Christian Albrechts University of Kiel RCV000050227 SCV000082806 not provided Deficiency of steroid 11-beta-monooxygenase no assertion provided not provided
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV000050227 SCV004099438 pathogenic Deficiency of steroid 11-beta-monooxygenase 2023-10-30 no assertion criteria provided clinical testing

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