Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Prevention |
RCV000721256 | SCV000852274 | likely pathogenic | not provided | 2015-10-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001067312 | SCV001232366 | pathogenic | RYR1-related disorder | 2023-09-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln3977*) in the RYR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 23919265, 25960145, 28818389, 30611313). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 590392). |
| Victorian Clinical Genetics Services, |
RCV004788145 | SCV005399339 | pathogenic | RYR1-related myopathy | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0103 - Both loss- and gain-of-function are known mechanisms of disease for this gene (PMID: 23919265). (N) 0108 - This gene is known to be associated with both recessive and dominant disease (PMID: 23919265). (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 87 of 106). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Other variants predicted to cause NMD in this gene have been reported in ClinVar as pathogenic. (P) 0803 - Low previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported as likely pathogenic in a patient (ClinVar). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |
| All of Us Research Program, |
RCV003999814 | SCV004826455 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2023-08-15 | flagged submission | clinical testing | This variant changes 1 nucleotide in exon 87 of the RYR1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RYR1 function due to truncation variants is not an established disease mechanism for autosomal dominant malignant hyperthermia, although it is associated with other phenotype(s) (ClinVar Variation ID: 590392; clinicalgenome.org). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia. |