Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000003458 | SCV004298849 | uncertain significance | Neurofibromatosis, type 2 | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 62 of the NF2 protein (p.Phe62Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of NF2-related conditions (PMID: 8081368, 8757035; Invitae). ClinVar contains an entry for this variant (Variation ID: 3297). 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%. Experimental studies have shown that this missense change affects NF2 function (PMID: 12118253). 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. |
| OMIM | RCV000003458 | SCV000023616 | pathogenic | Neurofibromatosis, type 2 | 2002-08-01 | no assertion criteria provided | literature only |