Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV002256559 | SCV002526737 | uncertain significance | Charcot-Marie-Tooth disease type 2E | 2022-06-01 | criteria provided, single submitter | clinical testing | _x000D_ Criteria applied: PM1, PM2_SUP |
Labcorp Genetics |
RCV002256559 | SCV003446708 | uncertain significance | Charcot-Marie-Tooth disease type 2E | 2024-03-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 346 of the NEFL protein (p.Ala346Asp). 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. ClinVar contains an entry for this variant (Variation ID: 695003). 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 with a negative predictive value of 80%. 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. |
Genesis Genome Database | RCV000857198 | SCV000999780 | uncertain significance | Charcot-Marie-Tooth disease | 2019-08-14 | no assertion criteria provided | research |