Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001377991 | SCV001575459 | pathogenic | Multiple endocrine neoplasia, type 1 | 2023-10-03 | criteria provided, single submitter | clinical testing | This variant results in the deletion of c.1351-3_1359del 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 been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 15714081). This variant is also known as Deletion CAGGTGCGGCAG . ClinVar contains an entry for this variant (Variation ID: 1066873). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Arg452Pro) have been determined to be pathogenic (PMID: 29036195; 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. |
| ARUP Laboratories, |
RCV001810728 | SCV002048656 | likely pathogenic | not provided | 2021-05-18 | criteria provided, single submitter | clinical testing | The MEN1 c.1351-3_1359del; p.? variant is reported in the literature in at least one family affected with multiple endocrine neoplasia type 1 (Klein 2005). This variant is also reported in ClinVar (Variation ID: 1066873), and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant deletes the canonical splice acceptor site of intron 9 and part of exon 10, which is likely to negatively impact gene function. Additionally, similar deletions of this splice site are reported in individuals and families affected with multiple endocrine neoplasia type 1 (Cardinal 2005, Jager 2006). Based on available information, this variant is considered to be likely pathogenic. References: Cardinal JW et al. A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing. J Med Genet. 2005 Jan;42(1):69-74. PMID: 15635078. Jager AC et al. Characteristics of the Danish families with multiple endocrine neoplasia type 1. Mol Cell Endocrinol. 2006 Apr 25;249(1-2):123-32. PMID: 16563611. Klein RD et al. Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic laboratory. Genet Med. 2005 Feb;7(2):131-8. PMID: 15714081. |