Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001047541 | SCV001211506 | pathogenic | Multiple endocrine neoplasia, type 1 | 2023-07-14 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 9 (c.1277_1350+28del) of the MEN1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 844638). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Trp436Arg) have been determined to be pathogenic (PMID: 21127195, 21819486; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |