ClinVar Miner

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

dbSNP: rs754572007
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519242 SCV000620189 pathogenic not provided 2024-12-10 criteria provided, single submitter clinical testing Reported as a secondary finding in a male individual with non-obstructive azoospermia (PMID: 35535697); 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; This variant is associated with the following publications: (PMID: 35535697)
Labcorp Genetics (formerly Invitae), Labcorp RCV000807652 SCV000947717 pathogenic RYR1-related disorder 2024-11-30 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
All of Us Research Program, National Institutes of Health RCV002259346 SCV005425343 uncertain significance Malignant hyperthermia, susceptibility to, 1 2024-08-06 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 90 of the RYR1 gene, creating a frameshift and 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: 451481). This variant has been identified in 10/249298 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of RYR1 function due to haploinsufficiency is not an established disease mechanism for autosomal dominant malignant hyperthermia. Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.