Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000456206 | SCV000563778 | pathogenic | Multiple endocrine neoplasia, type 1 | 2016-09-03 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon 10 of the MEN1 gene. The 5' boundary is likely confined to intron 9. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated MEN1 protein. While this particular variant has not been reported in the literature, truncating variants in MEN1 are known to be pathogenic (PMID: 17853334, 12112656). This deletion removes the functionally conserved nuclear localization signal of the MEN1 protein. Experimental studies have shown that disruption of this region abrogates the ability of MEN1 to bind DNA, regulate target gene expression, and inhibit cell proliferation (PMID: 15331604, 16449969). For these reasons, this variant has been classified as Pathogenic. |