ClinVar Miner

Submissions for variant NM_001005360.2(DNM2):c.1105C>T (p.Arg369Trp) (rs121909090)

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
Genetic Services Laboratory, University of Chicago RCV000145899 SCV000193036 pathogenic Myopathy, centronuclear 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000641108 SCV000762730 pathogenic Charcot-Marie-Tooth disease, dominant intermediate B 2018-08-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 369 of the DNM2 protein (p.Arg369Trp). 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 centronuclear myopathy (CNM) in several families (PMID: 16227997, 22613877). This variant has also been reported in individuals with CNM and cardiomyopathy (PMID: 25492887) as well as CNM with paravertebral muscles hypertrophy and mild neutropenia (PMID: 20817456). ClinVar contains an entry for this variant (Variation ID: 7280). Experimental studies have shown that this missense change leads to abnormally stable polymers and cytosolic aggregates (PMID: 24016602, 20529869). A mouse model for CNM carrying this missense change shows reduced de novo actin filament formation, increased cytosolic aggregates and impaired actin dependent trafficking (PMID: 28676641). A different missense substitution at this codon (p.Arg369Gln) has been determined to be pathogenic (PMID: 16227997, 25501959). This suggests that the arginine residue is critical for DNM2 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007703 SCV000027904 pathogenic Myopathy, centronuclear, 1 2005-11-01 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.