ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.14129+1G>A

gnomAD frequency: 0.00001  dbSNP: rs142929172
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519097 SCV000617962 likely pathogenic not provided 2024-01-22 criteria provided, single submitter clinical testing 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.; Has not been previously published as pathogenic or benign to our knowledge
Revvity Omics, Revvity RCV000519097 SCV002019939 likely pathogenic not provided 2022-04-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001851492 SCV002305243 likely pathogenic RYR1-related disorder 2023-07-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 96 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 present in population databases (rs142929172, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 449641). 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 RCV002497013 SCV002809362 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 2021-07-07 criteria provided, single submitter clinical testing

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