ClinVar Miner

Submissions for variant NM_001005361.3(DNM2):c.1564C>T (p.Arg522Cys)

dbSNP: rs2072577342
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
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268099 SCV001446753 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Invitae RCV001880160 SCV002303573 likely pathogenic Charcot-Marie-Tooth disease dominant intermediate B 2022-08-09 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 522 of the DNM2 protein (p.Arg522Cys). This missense change has been observed in individual(s) with centronuclear myopathy (PMID: 22396310). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg522 amino acid residue in DNM2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20227276, 22396310, 24465259, 25501959, 25957634, 26908122). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 DNM2 protein function. ClinVar contains an entry for this variant (Variation ID: 986927).
Inherited Neuropathy Consortium Ii, University Of Miami RCV001880160 SCV004174749 uncertain significance Charcot-Marie-Tooth disease dominant intermediate B 2016-01-06 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.