Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000552063 | SCV000628855 | uncertain significance | Neurofibromatosis, type 2 | 2017-05-30 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on NF2 function. The available evidence is currently insufficient to determine its role 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with a NF2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with arginine at codon 495 of the NF2 protein (p.Ile495Arg). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and arginine. |