Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001244541 | SCV001417768 | uncertain significance | Neurofibromatosis, type 2 | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 225 of the NF2 protein (p.Arg225Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 969242). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV002366076 | SCV002666965 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-04 | criteria provided, single submitter | clinical testing | The p.R225W variant (also known as c.673C>T), located in coding exon 7 of the NF2 gene, results from a C to T substitution at nucleotide position 673. The arginine at codon 225 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV001244541 | SCV003815869 | uncertain significance | Neurofibromatosis, type 2 | 2022-02-21 | criteria provided, single submitter | clinical testing |