Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Prevention |
RCV000721483 | SCV000852555 | pathogenic | not provided | 2019-04-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001385700 | SCV001585659 | pathogenic | RYR1-related disorder | 2022-02-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 201146). This premature translational stop signal has been observed in individual(s) with congenital myopathy with fiber-type disproportion (PMID: 28357410, 31127727). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg997*) 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: 20583297, 20839240, 23919265, 28818389). |
| Revvity Omics, |
RCV000721483 | SCV002019935 | pathogenic | not provided | 2019-10-21 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003996722 | SCV004826640 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2023-12-18 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 24 of the RYR1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been reported in individuals affected with autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotype(s) (ClinVar variation ID: 201146). This variant has been identified in 1/249108 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) (clinicalgenome.org; ClinVar variation ID: 201146). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia. |