ClinVar Miner

Submissions for variant NM_000497.4(CYP11B1):c.1361G>A (p.Arg454His)

gnomAD frequency: 0.00001  dbSNP: rs367634557
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672406 SCV000797506 likely pathogenic Deficiency of steroid 11-beta-monooxygenase 2018-01-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002531315 SCV003440818 pathogenic not provided 2022-04-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg454 amino acid residue in CYP11B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20529578, 20947076, 22964742, 25911436). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 556405). This missense change has been observed in individuals with autosomal recessive CYP11B1-related conditions (PMID: 25911436). This variant is present in population databases (rs367634557, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 454 of the CYP11B1 protein (p.Arg454His).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526748 SCV005039791 pathogenic Congenital adrenal hyperplasia 2024-03-19 criteria provided, single submitter clinical testing Variant summary: CYP11B1 c.1361G>A (p.Arg454His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251224 control chromosomes. c.1361G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Steroid 11b-hydroxylase deficiency (e.g. Wang_2015, Xie_2022). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25911436, 35685215). ClinVar contains an entry for this variant (Variation ID: 556405). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005046898 SCV005679861 likely pathogenic Deficiency of steroid 11-beta-monooxygenase; Glucocorticoid-remediable aldosteronism 2024-03-15 criteria provided, single submitter clinical testing

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