Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001346791 | SCV001541017 | uncertain significance | Neurofibromatosis, type 2 | 2020-07-23 | 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 create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 308 of the NF2 protein (p.Met308Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. |
Ambry Genetics | RCV002377471 | SCV002686791 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-28 | criteria provided, single submitter | clinical testing | The p.M308V variant (also known as c.922A>G), located in coding exon 10 of the NF2 gene, results from an A to G substitution at nucleotide position 922. The methionine at codon 308 is replaced by valine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |