ClinVar Miner

Submissions for variant NM_001927.4(DES):c.1A>G (p.Met1Val) (rs1057523274)

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
GeneDx RCV000417495 SCV000531325 likely pathogenic not provided 2016-09-02 criteria provided, single submitter clinical testing The c.1A>G variant in the DES gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. As this variant changes the translation initiator Methionine codon, the resultant protein is described as p.Met1?, using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. The c.1A>G variant was not observed in approximately 5,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1A>G as a likely pathogenic variant.
Genetic Services Laboratory, University of Chicago RCV000502195 SCV000594355 likely pathogenic Myofibrillar myopathy 1 2016-12-07 criteria provided, single submitter clinical testing
Invitae RCV001217218 SCV001389052 likely pathogenic Myofibrillar myopathy 1; Muscular dystrophy, limb-girdle, type 2R 2019-11-12 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the DES mRNA. The next in-frame methionine is located at codon 263. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DES-related conditions. ClinVar contains an entry for this variant (Variation ID: 388926). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Ser12 amino acid residue in DES. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20696008, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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.