Submissions for variant NM_000540.3(RYR1):c.12319del (p.Ile4107fs)

dbSNP: rs754572007

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519242	SCV000620189	pathogenic	not provided	2023-03-31	criteria provided, single submitter	clinical testing	Frameshift 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; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000807652	SCV000947717	pathogenic	RYR1-related disorder	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile4107Serfs*15) 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 (rs754572007, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 451481). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000519242	SCV002019926	likely pathogenic	not provided	2022-05-31	criteria provided, single submitter	clinical testing
Laan Lab, Human Genetics Research Group, University of Tartu	RCV002259346	SCV002538619	pathogenic	Malignant hyperthermia, susceptibility to, 1	2021-05-01	criteria provided, single submitter	research
Fulgent Genetics, Fulgent Genetics	RCV002497026	SCV002811563	likely pathogenic	Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome	2021-10-17	criteria provided, single submitter	clinical testing