ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.2683-1G>A

dbSNP: rs2145434598
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002226026 SCV002504009 pathogenic not provided 2022-03-21 criteria provided, single submitter clinical testing Reported in an individual with distal arthrogryposis who also harbored an RYR1 missense variant (Chong et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25683120)
Labcorp Genetics (formerly Invitae), Labcorp RCV003089201 SCV003443234 likely pathogenic RYR1-related disorder 2023-10-11 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 21 of the RYR1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RYR1 are known to be pathogenic (PMID: 23919265, 25960145, 28818389, 30611313). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of RYR1-related conditions (PMID: 25683120). ClinVar contains an entry for this variant (Variation ID: 1678712). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.