Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000632649 | SCV000753835 | uncertain significance | Neurofibromatosis, type 2 | 2020-07-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 589 of the NF2 protein (p.Val589Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; 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 | RCV001013030 | SCV001173562 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-11 | criteria provided, single submitter | clinical testing | The p.V589M variant (also known as c.1765G>A), located in coding exon 16 of the NF2 gene, results from a G to A substitution at nucleotide position 1765. The valine at codon 589 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |