Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV001172734 | SCV001335800 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Invitae | RCV003514468 | SCV004344007 | uncertain significance | Charcot-Marie-Tooth disease type 2E | 2023-05-14 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 79 of the NEFL protein (p.Ile79Val). This variant is present in population databases (rs765260132, gnomAD 0.003%). 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. 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 not expected to disrupt NEFL protein function. ClinVar contains an entry for this variant (Variation ID: 916806). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32376792). |