Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001235388 | SCV001408070 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2019-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces Valine with Methionine at codon 434 of the MEN1 protein (p.Val434Met). The Valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs757803925, ExAC 0.002%). This variant has not been reported in the literature in individuals with MEN1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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 | RCV003166453 | SCV003860279 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | The p.V434M variant (also known as c.1300G>A), located in coding exon 8 of the MEN1 gene, results from a G to A substitution at nucleotide position 1300. The valine at codon 434 is replaced by methionine, 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. |