Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000525596 | SCV000628873 | uncertain significance | Neurofibromatosis, type 2 | 2023-04-19 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt NF2 protein function. ClinVar contains an entry for this variant (Variation ID: 457919). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 187 of the NF2 protein (p.Arg187Lys). |
Ambry Genetics | RCV002350193 | SCV002648378 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-22 | criteria provided, single submitter | clinical testing | The p.R187K variant (also known as c.560G>A), located in coding exon 6 of the NF2 gene, results from a G to A substitution at nucleotide position 560. The arginine at codon 187 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is 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. |
Gene |
RCV003324760 | SCV004030601 | uncertain significance | not provided | 2023-02-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |