ClinVar Miner

Submissions for variant NM_000497.3(CYP11B1):c.953C>G (p.Thr318Arg) (rs104894061)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672570 SCV000797684 likely pathogenic Deficiency of steroid 11-beta-monooxygenase 2018-02-06 criteria provided, single submitter clinical testing
Invitae RCV001224692 SCV001396907 pathogenic not provided 2019-06-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 318 of the CYP11B1 protein (p.Thr318Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another CYP11B1 variant in several individuals affected with congenital adrenal hyperplasia due to 11 -hydroxylase deficiency (PMID: 9435454, 28228528, 16046588, 26476331). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 556549). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Thr318 amino acid residue in CYP11B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10487675, 8506298). 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.

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