Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001219319 | SCV001391252 | uncertain significance | Neurofibromatosis, type 2 | 2023-08-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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: 948122). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 245 of the NF2 protein (p.Asp245Asn). |
Ambry Genetics | RCV002379827 | SCV002671087 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | The p.D245N variant (also known as c.733G>A), located in coding exon 8 of the NF2 gene, results from a G to A substitution at nucleotide position 733. The aspartic acid at codon 245 is replaced by asparagine, 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. |