Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001313568 | SCV001504068 | uncertain significance | Neurofibromatosis, type 2 | 2023-06-25 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 expected to disrupt NF2 protein function. ClinVar contains an entry for this variant (Variation ID: 1014785). This variant has not been reported in the literature in individuals affected with NF2-related conditions. 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 sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 218 of the NF2 protein (p.Gly218Cys). |
Ambry Genetics | RCV002366162 | SCV002657935 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-03 | criteria provided, single submitter | clinical testing | The p.G218C variant (also known as c.652G>T), located in coding exon 7 of the NF2 gene, results from a G to T substitution at nucleotide position 652. The glycine at codon 218 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV003317476 | SCV004021796 | uncertain significance | not provided | 2023-01-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11756419, 16324214, Javaid2021[Computational]) |