Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002362542 | SCV002664418 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-03 | criteria provided, single submitter | clinical testing | The p.K233Q variant (also known as c.697A>C), located in coding exon 3 of the MEN1 gene, results from an A to C substitution at nucleotide position 697. The lysine at codon 233 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003098432 | SCV003003475 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2021-12-30 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 233 of the MEN1 protein (p.Lys233Gln). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |