ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.7835+1G>A

dbSNP: rs1057524858
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000442837 SCV000536646 likely pathogenic not provided 2017-02-01 criteria provided, single submitter clinical testing The c.7835+1G>A variant in the RYR1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 48. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.7835+1G>A variant was not observed in approximately 6,500 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.7835+1G>A as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001865407 SCV002265954 likely pathogenic RYR1-related disorder 2021-08-18 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 48 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: 20583297, 20839240, 23919265, 28818389). This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with RYR1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 393262). 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.
Fulgent Genetics, Fulgent Genetics RCV002488988 SCV002793416 likely pathogenic Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-12-07 criteria provided, single submitter clinical testing

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