Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001050468 | SCV001214576 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 544 of the MEN1 protein (p.Pro544Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of multiple endocrine neoplasia type 1 (PMID: 10849016). ClinVar contains an entry for this variant (Variation ID: 847015). 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. |
Ambry Genetics | RCV004031565 | SCV005030383 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-01 | criteria provided, single submitter | clinical testing | The p.P544S variant (also known as c.1630C>T), located in coding exon 9 of the MEN1 gene, results from a C to T substitution at nucleotide position 1630. The proline at codon 544 is replaced by serine, an amino acid with similar properties. This variant (designated as C>>T at 1740) has been reported in a patient with multiple endocrine neoplasia type 1 (MEN1) (Roijers JF et al. Eur J Clin Invest, 2000 Jun;30:487-92). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Clinical Genetics Laboratory, |
RCV001529168 | SCV005199114 | uncertain significance | not provided | 2022-12-15 | criteria provided, single submitter | clinical testing | |
Diagnostic Laboratory, |
RCV001529168 | SCV001742178 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV001529168 | SCV001932606 | uncertain significance | not provided | no assertion criteria provided | clinical testing |