Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001234174 | SCV001406806 | uncertain significance | Neurofibromatosis, type 2 | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 554 of the NF2 protein (p.Arg554Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 960618). 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 not expected to disrupt NF2 protein function with a negative 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 | RCV002402733 | SCV002706537 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-01 | criteria provided, single submitter | clinical testing | The p.R554K variant (also known as c.1661G>A), located in coding exon 15 of the NF2 gene, results from a G to A substitution at nucleotide position 1661. The arginine at codon 554 is replaced by lysine, 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. |
| Prevention |
RCV003983854 | SCV004796893 | uncertain significance | NF2-related disorder | 2024-02-26 | criteria provided, single submitter | clinical testing | The NF2 c.1661G>A variant is predicted to result in the amino acid substitution p.Arg554Lys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| All of Us Research Program, |
RCV001234174 | SCV004843150 | uncertain significance | Neurofibromatosis, type 2 | 2023-11-30 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004570590 | SCV005052373 | uncertain significance | Familial meningioma | 2024-01-05 | criteria provided, single submitter | clinical testing |