Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001057973 | SCV001222504 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2022-10-17 | criteria provided, single submitter | clinical testing | 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: 853205). 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 not expected to disrupt MEN1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 521 of the MEN1 protein (p.Thr521Pro). |
| Ambry Genetics | RCV002402418 | SCV002708903 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-27 | criteria provided, single submitter | clinical testing | The p.T521P variant (also known as c.1561A>C), located in coding exon 9 of the MEN1 gene, results from an A to C substitution at nucleotide position 1561. The threonine at codon 521 is replaced by proline, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |