Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001367302 | SCV001563648 | uncertain significance | Neurofibromatosis, type 2 | 2023-07-06 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF2 protein function. ClinVar contains an entry for this variant (Variation ID: 1058201). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 126 of the NF2 protein (p.Ile126Val). |
| Ambry Genetics | RCV002350696 | SCV002623208 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-16 | criteria provided, single submitter | clinical testing | The p.I126V variant (also known as c.376A>G), located in coding exon 4 of the NF2 gene, results from an A to G substitution at nucleotide position 376. The isoleucine at codon 126 is replaced by valine, 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. |
| Baylor Genetics | RCV004570899 | SCV005052375 | uncertain significance | Familial meningioma | 2023-12-20 | criteria provided, single submitter | clinical testing |