Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000680086 | SCV000807526 | pathogenic | Central core myopathy | 2017-09-01 | criteria provided, single submitter | clinical testing | This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in trans with a missense variant in a 5-year-old female with global delays, hypertonia, seizure, delayed myelination, mild scoliosis, elevated CK |
| Revvity Omics, |
RCV001784304 | SCV002019975 | pathogenic | not provided | 2020-07-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001861877 | SCV002122971 | pathogenic | RYR1-related disorder | 2023-12-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln70*) 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 is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with autosomal recessive RYR1-related conditions (PMID: 29298851). ClinVar contains an entry for this variant (Variation ID: 561100). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002507180 | SCV002815334 | pathogenic | Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome | 2021-07-28 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004004220 | SCV004820705 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2023-08-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 3 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 with autosomal dominant malignant hyperthermia in the literature. This variant has been identified in 1/251234 chromosomes 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: 561100). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia. |