ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.7858C>T (p.Gln2620Ter)

gnomAD frequency: 0.00001  dbSNP: rs1365856881
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001219907 SCV001391872 pathogenic RYR1-related disorder 2023-08-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2620*) 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 multi-minicore disease (PMID: 25960145; Invitae). ClinVar contains an entry for this variant (Variation ID: 948615). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001780144 SCV002019951 pathogenic not provided 2019-09-26 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002491686 SCV002785808 pathogenic Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-10-16 criteria provided, single submitter clinical testing
GeneDx RCV001780144 SCV005325374 likely pathogenic not provided 2024-02-07 criteria provided, single submitter clinical testing Reported in published literature in a patient with multiminicore disease who also harbored the R3539H variant in RYR1, which is classified as likely benign by GeneDx; familial segregation analysis was not performed (PMID: 25960145); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25960145)
Developmental and Behavioral Pediatrics, First Affiliated Hospital of Jilin University RCV003156321 SCV002576303 likely pathogenic Central core myopathy no assertion criteria provided provider interpretation

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