Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660040 | SCV000781992 | uncertain significance | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000660040 | SCV004428136 | uncertain significance | Neurofibromatosis, type 1 | 2023-01-20 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Met1215 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26740943; 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. ClinVar contains an entry for this variant (Variation ID: 547631). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1215 of the NF1 protein (p.Met1215Thr). |