ClinVar Miner

Submissions for variant NM_001927.4(DES):c.735+1G>A (rs397516698)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037249 SCV000060906 likely pathogenic Myofibrillar myopathy 1 2017-05-22 criteria provided, single submitter clinical testing The c.735+1G>A variant in DES has been reported in at least 2 individuals with d esminopathy (Shatunov et al., unpublished data; reviewed by Goldfarb 2004, Gudko va 2013, LMM data), and was absent from large population studies. This variant o ccurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Ad ditional variants affecting splicing of this exon have been reported in individu als with desminopathy including a different variant at the same position (c.7351 +G>C LMM data: variant occurred de novo) and c.735+3A>G (identified in 6 individ uals with desminopathy and segregated in 9 individuals from 2 families: Park 200 0, Dalakas 2000, Wahni 2012, Greenberg 2012, McDonald 2012, Gudkova 2013, LMM un published data). In summary, although additional studies are required to fully e stablish its clinical significance, the c.735+1G>A variant is likely pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000393713 SCV000343204 pathogenic not provided 2016-06-23 criteria provided, single submitter clinical testing
Invitae RCV001220792 SCV001392803 pathogenic Myofibrillar myopathy 1; Muscular dystrophy, limb-girdle, type 2R 2019-05-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the DES gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in several individuals affected with clinical features of autosomal dominant desminopathy (PMID: 30614851, 28703267). ClinVar contains an entry for this variant (Variation ID: 44268). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 29034897). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DES are known to be pathogenic (PMID: 23575897). For these reasons, this variant has been classified as Pathogenic.
Genomics England Pilot Project,Genomics England RCV000037249 SCV001760073 likely pathogenic Myofibrillar myopathy 1 no assertion criteria provided 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.