Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000557509 | SCV000628858 | uncertain significance | Neurofibromatosis, type 2 | 2019-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 567 of the NF2 protein (p.Asp567Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (no rsID, ExAC 0.05%). This variant has not been reported in the literature in individuals with NF2-related disease. ClinVar contains an entry for this variant (Variation ID: 457904). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on NF2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV000765631 | SCV000896956 | uncertain significance | Meningioma, familial; Neurofibromatosis, type 2; Schwannomatosis 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001012778 | SCV001173278 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-24 | criteria provided, single submitter | clinical testing | The p.D567E variant (also known as c.1701C>G), located in coding exon 15 of the NF2 gene, results from a C to G substitution at nucleotide position 1701. The aspartic acid at codon 567 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well 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. |