ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.1262G>A (p.Arg421Gln) (rs587783772)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000146393 SCV000992789 pathogenic Severe X-linked myotubular myopathy 2017-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000428593 SCV000516968 pathogenic not provided 2017-09-07 criteria provided, single submitter clinical testing The p.R421Q substitution has been reported in multiple individuals and has been reported previously as amaternally inherited variant in an individual with severe myotubular myopathy, and supportive histologicalfindings on muscle biopsy (Koga et al., 2012). Crystallography has shown that R421 is located within thephosphatase domain and functional studies showed that p.R421Q eliminated phosphatase activity (Goryunovet al., 2008). This substitution occurs at a position that is conserved across species, and multiple variants have been reported in nearby residues in association with myotubular myopathy (Stenson et al., 2009).Therefore, p.R421Q is considered a pathogenic variant.
Genetic Services Laboratory, University of Chicago RCV000146393 SCV000193679 pathogenic Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000146393 SCV000634484 pathogenic Severe X-linked myotubular myopathy 2017-02-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 421 of the MTM1 protein (p.Arg421Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (rs587783772, ExAC no frequency). This variant has been reported in multiple individuals affected with myotubular myopathy and is associated with a severe phenotype (PMID: 22520358, 9285787, 9305655, 11793470, 10790201). ClinVar contains an entry for this variant (Variation ID: 158914). Experimental studies have shown that this missense change significantly impairs phosphatase activity in vitro and in vivo (PMID: 23071445, 12646134, 23917616, 21135508, 17973976). For these reasons, this variant has been classified as Pathogenic.

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.