Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001037823 | SCV001201255 | pathogenic | Multiple endocrine neoplasia, type 1 | 2023-07-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly401Valfs*44) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 210 amino acid(s) of the MEN1 protein. 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: 836644). This variant disrupts the NLS2 domain of the MEN1 protein, which is important for DNA binding and repression of cell proliferation (PMID: 15331604, 16449969). While functional studies have not been performed to directly test the effect of this variant on MEN1 protein function, this suggests that disruption of this region of the protein is causative of disease. This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Lys559Glufs*38) have been determined to be pathogenic (PMID: 10090472; 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. |
| Ambry Genetics | RCV002346250 | SCV002650086 | pathogenic | Hereditary cancer-predisposing syndrome | 2015-09-04 | criteria provided, single submitter | clinical testing | The c.1202delG pathogenic mutation, located in coding exon 8 of the MEN1 gene, results from a deletion of one nucleotide at position 1202, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |