Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000709157 | SCV000838452 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000709157 | SCV001387923 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 469 of the MEN1 protein (p.Glu469Ala). 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: 584769). 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 | RCV002388350 | SCV002699187 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-10 | criteria provided, single submitter | clinical testing | The p.E469A variant (also known as c.1406A>C), located in coding exon 9 of the MEN1 gene, results from an A to C substitution at nucleotide position 1406. The glutamic acid at codon 469 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |