ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.8589T>C (p.Ser2863=)

gnomAD frequency: 0.32548  dbSNP: rs2229146
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Total submissions: 21
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Congenital Myopathies Variant Curation Expert Panel, ClinGen RCV004737187 SCV005367850 benign RYR1-related myopathy 2024-08-07 reviewed by expert panel curation The c.8589T>C (p.Ser2863=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by UCSC Genome Browser (BP4, BP7). The filtering allele frequency (the lower threshold of the 95% CI of 40732/91032, 9442 homozygotes) of the c.8589T>C variant in RYR1 is 0.4430 for South Asian chromosomes by gnomAD v4.1, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.00697) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for RYR1-related myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BA1, BP4, BP7. (Congenital Myopathies VCEP specifications version 1; 8/7/2024)
Eurofins Ntd Llc (ga) RCV000079178 SCV000111047 benign not specified 2014-06-06 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000079178 SCV000194874 benign not specified 2013-08-15 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000079178 SCV000269791 benign not specified 2015-01-13 criteria provided, single submitter clinical testing p.Ser2863Ser in exon 55 of RYR1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 43.0% (1893/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2229146).
PreventionGenetics, part of Exact Sciences RCV000079178 SCV000305051 benign not specified 2018-04-03 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000281789 SCV000412584 benign Central core myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000339193 SCV000412585 benign Malignant hyperthermia, susceptibility to, 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000403926 SCV000412586 benign Congenital multicore myopathy with external ophthalmoplegia 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000304127 SCV000412587 benign Neuromuscular disease, congenital, with uniform type 1 fiber 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000079178 SCV000519604 benign not specified 2016-01-25 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001514067 SCV001721816 benign RYR1-related disorder 2024-02-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000281789 SCV002032952 benign Central core myopathy 2021-11-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001795076 SCV002032953 benign King Denborough syndrome 2021-11-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000403926 SCV002032954 benign Congenital multicore myopathy with external ophthalmoplegia 2021-11-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002490688 SCV002794622 benign Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-10-08 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000339193 SCV004358157 benign Malignant hyperthermia, susceptibility to, 1 2019-03-29 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV000119753 SCV005310839 benign not provided criteria provided, single submitter not provided
Leiden Muscular Dystrophy (RYR1) RCV000119753 SCV000154660 not provided not provided no assertion provided not provided
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000119753 SCV001554217 uncertain significance not provided no assertion criteria provided clinical testing Allele frequency is common in at least one population database (frequency: 45.825% in gnomAD_Exomes) based on the frequency threshold of 2.223% for this gene. Variant was observed in a homozygous state in population databases more than expected for disease. 9 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation. A synonymous variant not located in a splice region.
Clinical Genetics, Academic Medical Center RCV000079178 SCV001921729 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000079178 SCV001951442 benign not specified no assertion criteria provided clinical testing

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