ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14304-6C>A (rs794728693)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182600 SCV000234958 uncertain significance not provided 2016-09-22 criteria provided, single submitter clinical testing The c.14304-6 C>A variant in the RYR1 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. The c.14304-6 C>A splice site variant damages the natural splice acceptor site in intron 98. In silico algorithms predict this variant may result in 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.14304-6 C>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.14304-6 C>A as a variant of unknown significance. This variant has been observed to be maternally inherited. The variant is found in RYR1 panel(s).
Invitae RCV000702407 SCV000831260 uncertain significance RYR1-Related Disorders 2018-03-15 criteria provided, single submitter clinical testing This sequence change falls in intron 98 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: 201143). 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.

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