Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660115 | SCV000782099 | uncertain significance | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000660115 | SCV003241632 | pathogenic | Neurofibromatosis, type 1 | 2022-11-06 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 547692). This missense change has been observed in individual(s) with neurofibromatosis type 1 (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2365 of the NF1 protein (p.Phe2365Ser). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Phe2365 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |