Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001899811 | SCV002126229 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2020-12-31 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 496 of the MEN1 protein (p.Lys496Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has not been reported in the literature in individuals with MEN1-related conditions. |
Ambry Genetics | RCV003164132 | SCV003860294 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-25 | criteria provided, single submitter | clinical testing | The p.K496R variant (also known as c.1487A>G), located in coding exon 9 of the MEN1 gene, results from an A to G substitution at nucleotide position 1487. The lysine at codon 496 is replaced by arginine, an amino acid with highly 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. |
All of Us Research Program, |
RCV001899811 | SCV004837631 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-11-30 | criteria provided, single submitter | clinical testing |