ClinVar Miner

Submissions for variant NM_001303256.3(MORC2):c.754C>T (p.Arg252Trp) (rs864309503)

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 RCV000202547 SCV000655834 pathogenic Charcot-Marie-Tooth disease, axonal, type 2z 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 190 of the MORC2 protein (p.Arg190Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with disease in multiple families affected with Charcot-Marie-Tooth disease, type 2 (CMT2) (PMID: 26497905, 26659848). It has also been reported in sporadic cases of CMT2 (PMID: 26497905, 26912637, 27105987), two of which were reported to have arisen de novo in the affected individuals. 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. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000624201 SCV000742292 pathogenic Inborn genetic diseases 2017-03-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
OMIM RCV000202547 SCV000257499 pathogenic Charcot-Marie-Tooth disease, axonal, type 2z 2015-10-24 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.