ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.7028-10G>A (rs1005260620)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000721631 SCV000619376 uncertain significance not provided 2017-07-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR1 gene. The c.7028-10 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.7028-10 G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.7028-10 G>A creates a cryptic acceptor site for intron 43 which may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000796862 SCV000936394 uncertain significance RYR1-Related Disorders 2018-10-10 criteria provided, single submitter clinical testing This sequence change falls in intron 43 of the RYR1 gene. It does not directly change the encoded amino acid sequence of the RYR1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RYR1-related disease. ClinVar contains an entry for this variant (Variation ID: 450762). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics RCV000721631 SCV000852741 uncertain significance not provided 2017-10-20 criteria provided, single submitter clinical testing

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