Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011983 | SCV001172380 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-23 | criteria provided, single submitter | clinical testing | The c.1539delA variant, located in coding exon 9 of the MEN1 gene, results from a deletion of one nucleotide at nucleotide position 1539, causing a translational frameshift with a predicted alternate stop codon (p.R516Gfs*43). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of MEN1, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 95 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time, however this alteration is expected to result in loss of function by premature protein truncation. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV001860686 | SCV002235758 | pathogenic | Multiple endocrine neoplasia, type 1 | 2021-05-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg516Glyfs*43) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 95 amino acid(s) of the MEN1 protein. This variant is not present in population databases (ExAC no frequency). This frameshift change has been reported in individuals and families affected with multiple endocrine neoplasia type 1, or related disorders (PMID: 9215689, 12112656, 12213668, 15670192, 17065424, 17853334, 23321498). It is considered to be a recurrent pathogenic mutation (PMID: 17879353). ClinVar contains an entry for this variant (Variation ID: 819433). For these reasons, this variant has been classified as Pathogenic. |