Submissions for variant NM_000540.3(RYR1):c.8337G>A (p.Glu2779=)

gnomAD frequency: 0.32150  dbSNP: rs2915952

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079177	SCV000111046	benign	not specified	2014-06-06	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000079177	SCV000194872	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000079177	SCV000269790	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Glu2779Glu in exon 53 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 42.7% (1879/4404) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2915952).
PreventionGenetics, part of Exact Sciences	RCV000079177	SCV000305044	benign	not specified	2018-04-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000344459	SCV000412559	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	RCV000383245	SCV000412560	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	RCV000293580	SCV000412561	benign	Central core myopathy	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	RCV000348376	SCV000412562	benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000079177	SCV000518234	benign	not specified	2016-01-13	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.
Invitae	RCV001514066	SCV001721815	benign	RYR1-Related Disorders	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000293580	SCV002032938	benign	Central core myopathy	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001795075	SCV002032939	benign	King Denborough syndrome	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000344459	SCV002032941	benign	Congenital multicore myopathy with external ophthalmoplegia	2021-11-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498392	SCV002805477	benign	Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000383245	SCV004358150	benign	Malignant hyperthermia, susceptibility to, 1	2019-03-29	criteria provided, single submitter	clinical testing
Leiden Muscular Dystrophy (RYR1)	RCV000119745	SCV000154652	not provided	not provided		no assertion provided	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000119745	SCV001552201	uncertain significance	not provided		no assertion criteria provided	clinical testing	Allele frequency is common in at least one population database (frequency: 46.041% in ExAC) 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	RCV000079177	SCV001922052	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079177	SCV001951837	benign	not specified		no assertion criteria provided	clinical testing