ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.497C>T (p.Ala166Val) (rs1557522849)

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 RCV000697586 SCV000826206 pathogenic Charcot-Marie-Tooth disease, type 2 2018-05-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 166 of the MFN2 protein (p.Ala166Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Charcot-Marie-Tooth disease in several families (PMID: 27862672, Invitae). 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. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000986242 SCV001135177 likely pathogenic Charcot-Marie-Tooth disease, type 2A2A 2019-05-28 criteria provided, single submitter clinical testing

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.