Total submissions: 3
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 | |
Gene |
RCV001548581 | SCV001768515 | likely benign | not provided | 2018-12-31 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
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. |