Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000810806 | SCV000951040 | likely pathogenic | Multiple endocrine neoplasia, type 1 | 2024-06-11 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 278 of the MEN1 protein (p.Met278Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with multiple endocrine neoplasia type 1 (Invitae). ClinVar contains an entry for this variant (Variation ID: 654780). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV004028709 | SCV005030517 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-08-27 | criteria provided, single submitter | clinical testing | The p.M278R variant (also known as c.833T>G), located in coding exon 5 of the MEN1 gene, results from a T to G substitution at nucleotide position 833. The methionine at codon 278 is replaced by arginine, an amino acid with similar properties. This variant has been observed in at least one individual with a personal history that is consistent with multiple endocrine neoplasia type 1 (MEN1) (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Mayo Clinic Laboratories, |
RCV004792507 | SCV005412363 | uncertain significance | not provided | 2024-08-19 | criteria provided, single submitter | clinical testing | PP3, PP4, PM2 |