Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012867 | SCV001173378 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-12 | criteria provided, single submitter | clinical testing | The p.N57K variant (also known as c.171C>A), located in coding exon 1 of the MEN1 gene, results from a C to A substitution at nucleotide position 171. The asparagine at codon 57 is replaced by lysine, an amino acid with similar properties. In a study of individuals with cutaneous melanoma and a history of two or more additional non-cutaneous independent cancer types undergoing whole exome sequencing or whole genome sequencing, this alteration was detected in none of the cases, but in 1/1358 controls (Pritchard AL et al. PLoS ONE, 2018 Apr;13:e0194098). 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. |
| Invitae | RCV001218098 | SCV001389967 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-04-15 | criteria provided, single submitter | clinical testing | 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. 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 expected to disrupt MEN1 protein function. ClinVar contains an entry for this variant (Variation ID: 819920). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 57 of the MEN1 protein (p.Asn57Lys). |