Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001063209 | SCV001228045 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-08-29 | criteria provided, single submitter | clinical testing | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 545 of the MEN1 protein (p.Pro545Ser). 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: 857520). |
| Ambry Genetics | RCV002402444 | SCV002704489 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-29 | criteria provided, single submitter | clinical testing | The p.P545S variant (also known as c.1633C>T), located in coding exon 9 of the MEN1 gene, results from a C to T substitution at nucleotide position 1633. The proline at codon 545 is replaced by serine, an amino acid with similar properties. This alteration has been reported in an individual with a clinical diagnosis of MEN1 (Crépin M et al. Electrophoresis, 2003 Jan;24:26-33). This alteration has also been reported in an individual with a pituitary adenoma (Cuny T et al. Eur. J. Endocrinol., 2013 Apr;168:533-41). Of note, this alteration is also reported as p.P540S, c.1618C>T in the literature. This amino acid position is highly conserved in available vertebrate species. 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. |