ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.275T>C (p.Leu92Pro) (rs1569816285)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001064640 SCV001229551 pathogenic Charcot-Marie-Tooth disease, type 2 2019-03-26 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 92 of the MFN2 protein (p.Leu92Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Charcot-Marie-Tooth disease and was observed to be de novo in at least one case (PMID: 16835246, 16714318). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Leu92 amino acid residue in MFN2. Other variant(s) that disrupt this residue (p.Leu92Arg) have been determined to be pathogenic (PMID: 21258814). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000790024 SCV000929414 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.