Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000711384 | SCV000841747 | pathogenic | not provided | 2024-10-17 | criteria provided, single submitter | clinical testing | This variant is located in a genomic region of low or unreliable sequencing quality, and therefore estimations of its population frequency are uninformative in assessment of variant pathogenicity (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This variant consists of three missense changes: p.Ile237Asn, p.Val238Glu, and p.Met240Lys, and has been referred to as the "exon 6 cluster" or the "E6 cluster" in published literature. In multiple individuals with congenital adrenal hyperplasia, this variant has been seen in trans with other recessive pathogenic variants in CYP21A2. Assessment of experimental evidence suggests this variant results in abnormal protein function. Experiments demonstrate this variant results in dramatically reduced enzymatic activity (PMID: 15623806). |
| Myriad Genetics, |
RCV000169566 | SCV001193773 | pathogenic | Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency | 2019-12-26 | criteria provided, single submitter | clinical testing | NM_000500.7(CYP21A2):c.(710T>A;713T>A;719T>A)(I237N;V238E;M240K) is classified as pathogenic in the context of congenital adrenal hyperplasia and is associated with the classic form of the disease. Sources cited for classification include the following: PMID 2845408, 23359698 and 2249999. Classification of NM_000500.7(CYP21A2):c.(710T>A;713T>A;719T>A)(I237N;V238E;M240K) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |