Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000701560 | SCV000830366 | uncertain significance | Neurofibromatosis, type 1 | 2021-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with proline at codon 2019 of the NF1 protein (p.Ser2019Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. 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. 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 NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 578527). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). |
Medical Genetics, |
RCV000701560 | SCV002567779 | likely pathogenic | Neurofibromatosis, type 1 | 2022-08-17 | criteria provided, single submitter | clinical testing |