ClinVar Miner

Submissions for variant NM_000497.4(CYP11B1):c.799G>A (p.Gly267Ser)

gnomAD frequency: 0.00001  dbSNP: rs1421641874
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV002249852 SCV002519466 pathogenic Glucocorticoid-remediable aldosteronism 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003094023 SCV003440820 likely pathogenic not provided 2022-04-16 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 267 of the CYP11B1 protein (p.Gly267Ser). RNA analysis indicates that this missense change induces altered splicing and likely results in the loss of 45 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This missense change has been observed in individuals with adrenal hyperplasia (PMID: 19567537, 25911436, 30242600, 32850530). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in the activation of a cryptic splice site in exon 4 (PMID: 19567537). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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