Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Human Genetics and Genomic Medicine, |
RCV003445469 | SCV004174191 | pathogenic | Charcot-Marie-Tooth disease type 2E | 2023-12-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003445469 | SCV004434658 | uncertain significance | Charcot-Marie-Tooth disease type 2E | 2023-02-10 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 98 of the NEFL protein (p.Asn98Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NEFL-related conditions. 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 NEFL protein function. This variant disrupts the p.Asn98 amino acid residue in NEFL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12477167, 12566280, 19158810, 21840889, 25448007, 26645395, 27206872). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |