ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.15036G>T (p.Trp5012Cys)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV002789971 SCV003761231 uncertain significance RYR1-related myopathy 2023-01-25 criteria provided, single submitter curation The heterozygous p.Trp5012Cys variant in RYR1 was identified by our study, in the compound heterozygous state with a variant of uncertain significance (ClinVar Variation ID: 544377), in one individual with central core disease. Familial segregation analysis revealed that this variant was in trans with a variant of uncertain significance (ClinVar Variation ID: 544377). The p.Trp5012Cys variant in RYR1 has not been previously reported in individuals with RYR1-related myopathy. This variant was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Trp5012Cys variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3 (Richards 2015).
All of Us Research Program, National Institutes of Health RCV004009557 SCV004834314 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces tryptophan with cysteine at codon 5012 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Athena Diagnostics RCV004999896 SCV005621268 uncertain significance not provided 2024-08-08 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. This variant has not been reported in large, multi-ethnic general populations. (http://gnomad.broadinstitute.org) Polyphen and MutationTaster predict this amino acid change may be damaging to the protein.

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.