Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001017136 | SCV001178169 | benign | Hereditary cancer-predisposing syndrome | 2022-09-09 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV001308827 | SCV001498298 | uncertain significance | Neurofibromatosis, type 2 | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 351 of the NF2 protein (p.Arg351Cys). This variant is present in population databases (rs747756728, gnomAD 0.01%). 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: 822078). 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 with a positive predictive value of 80%. 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. |
Genome- |
RCV001308827 | SCV002044875 | uncertain significance | Neurofibromatosis, type 2 | 2021-11-07 | criteria provided, single submitter | clinical testing |