Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000001244 | SCV000790308 | likely pathogenic | Deficiency of steroid 11-beta-monooxygenase | 2017-03-15 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000001244 | SCV000967661 | pathogenic | Deficiency of steroid 11-beta-monooxygenase | 2018-06-27 | criteria provided, single submitter | clinical testing | The p.Tyr423X variant in CYP11B1 has been reported in the compound heterozygote state in 1 individual with non-classic adrenal hyperplasia due to 11 beta-hydrox ylase deficiency (Joehrer 1997). This variant has been identified in 2/126704 Eu ropean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs267606755). This nonsense variant leads to a premature termination codon at position 423 which is predicted to lead to a truncated or a bsent protein. In summary, this variant meets criteria to be classified as patho genic for non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency in an autosomal recessive manner based upon a case report, low frequency in con trols and predicted impact on protein. Criteria applied: PVS1, PM2, PM3_Supporti ng. |
| Invitae | RCV001851530 | SCV002226157 | pathogenic | not provided | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr423*) in the CYP11B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP11B1 are known to be pathogenic (PMID: 8506298, 26476331). This variant is present in population databases (rs267606755, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with non-classic 11-beta-hydroxylase deficiency (PMID: 9302260). ClinVar contains an entry for this variant (Variation ID: 1185). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV000001244 | SCV002573252 | pathogenic | Deficiency of steroid 11-beta-monooxygenase | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000001185 / PMID: 9302260). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| Prevention |
RCV003415613 | SCV004116976 | pathogenic | CYP11B1-related disorder | 2022-11-18 | criteria provided, single submitter | clinical testing | The CYP11B1 c.1269T>G variant is predicted to result in premature protein termination (p.Tyr423*). This variant was reported in an individual with steroid-11 beta-hydroxylase deficiency (Joehrer et al. 1997. PubMed ID: 9302260). This variant is reported in 0.0015% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-143956502-A-C). Nonsense variants in CYP11B1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
| Baylor Genetics | RCV000001244 | SCV004215337 | pathogenic | Deficiency of steroid 11-beta-monooxygenase | 2024-03-11 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000001244 | SCV000021394 | pathogenic | Deficiency of steroid 11-beta-monooxygenase | 1997-10-01 | no assertion criteria provided | literature only |