Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000696206 | SCV000824758 | uncertain significance | Neurofibromatosis, type 2 | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 501 of the NF2 protein (p.Ile501Val). 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 574302). 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%). |
Ambry Genetics | RCV002388265 | SCV002699403 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-12 | criteria provided, single submitter | clinical testing | The p.I501V variant (also known as c.1501A>G), located in coding exon 14 of the NF2 gene, results from an A to G substitution at nucleotide position 1501. The isoleucine at codon 501 is replaced by valine, 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. |