Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000473350 | SCV000542221 | pathogenic | Neurofibromatosis, type 1 | 2020-01-03 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Ala330 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17311297, 23913538, 23758643). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. 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. This variant has been reported in an individual affected with neurofibromatosis type 1 (PMID: 27322474). ClinVar contains an entry for this variant (Variation ID: 404605). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 330 of the NF1 protein (p.Ala330Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. |
| Gene |
RCV003151771 | SCV003840458 | uncertain significance | not provided | 2023-01-04 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27322474) |