Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000810207 | SCV000950400 | uncertain significance | Neurofibromatosis, type 2 | 2023-12-15 | 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 467 of the NF2 protein (p.Arg467Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 654279). 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 | RCV001011380 | SCV001171690 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-15 | criteria provided, single submitter | clinical testing | The p.R467K variant (also known as c.1400G>A), located in coding exon 13 of the NF2 gene, results from a G to A substitution at nucleotide position 1400. The arginine at codon 467 is replaced by lysine, an amino acid with highly similar properties. 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. |
| Illumina Laboratory Services, |
RCV000810207 | SCV001306001 | uncertain significance | Neurofibromatosis, type 2 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Genome- |
RCV000810207 | SCV002044888 | uncertain significance | Neurofibromatosis, type 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003461192 | SCV004199055 | uncertain significance | Familial meningioma | 2023-07-31 | criteria provided, single submitter | clinical testing |