Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Medical Genetics, |
RCV002279174 | SCV002567790 | likely pathogenic | Neurofibromatosis, type 1 | 2022-08-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002279174 | SCV003232505 | likely pathogenic | Neurofibromatosis, type 1 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1987 of the NF1 protein (p.Asp1987Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1702856). 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 with a positive predictive value of 95%. This variant disrupts the p.Asp1987 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae; external communication). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |