ClinVar Miner

Submissions for variant NM_006158.5(NEFL):c.292A>G (p.Asn98Asp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen 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.

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