ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.7446T>C (p.Asp2482=)

gnomAD frequency: 0.00001  dbSNP: rs374058542
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000868129 SCV001009427 likely benign RYR1-Related Disorders 2023-07-28 criteria provided, single submitter clinical testing
GeneDx RCV001548581 SCV001768515 likely benign not provided 2018-12-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003387942 SCV004100015 uncertain significance not specified 2023-09-20 criteria provided, single submitter clinical testing Variant summary: RYR1 c.7446T>C (p.Asp2482Asp) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 3/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251222 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7446T>C in individuals affected with Malignant Hyperthermia Susceptibility and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014, and both classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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