ClinVar Miner

Submissions for variant NM_006158.4(NEFL):c.1319C>T (p.Pro440Leu) (rs587777882)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001044771 SCV001208586 pathogenic Charcot-Marie-Tooth disease type 2E 2019-07-03 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 440 of the NEFL protein (p.Pro440Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with autosomal dominant Charcot-Marie-Tooth (CMT) disease in a family (PMID: 25802885) and has been reported in unrelated individuals affected with CMT (PMID: 21149811, 30373780). ClinVar contains an entry for this variant (Variation ID: 155738). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.
Northcott Neuroscience Laboratory, ANZAC Research Institute RCV000143808 SCV000188701 probable-pathogenic not provided no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Inherited Neuropathy Consortium RCV000789071 SCV000928420 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.