Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001201836 | SCV001372927 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 380 of the MEN1 protein (p.Ala380Thr). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 933592). 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 with a positive predictive value of 80%. 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 | RCV002322000 | SCV002605630 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-24 | criteria provided, single submitter | clinical testing | The p.A380T variant (also known as c.1138G>A), located in coding exon 7 of the MEN1 gene, results from a G to A substitution at nucleotide position 1138. The alanine at codon 380 is replaced by threonine, an amino acid with similar properties. In one study which performed structural analysis for MEN1 missense variants, this alteration did not meet the threshold for pathogenicity (Caswell RC et al. J Endocr Soc, 2019 Dec;3:2258-2275). 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. |
| Baylor Genetics | RCV001201836 | SCV004194451 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-09-02 | criteria provided, single submitter | clinical testing |