Submissions for variant NM_000540.3(RYR1):c.7835+5A>G

gnomAD frequency: 0.38217  dbSNP: rs1469695

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079170	SCV000111039	benign	not specified	2014-06-06	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000079170	SCV000194862	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000079170	SCV000269784	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	c.7835+5A>G in intron 48 of RYR1: This variant is not expected to have clinical significance because it has been identified in 44.2% (1949/4406) of African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs1469695).
PreventionGenetics, part of Exact Sciences	RCV000079170	SCV000305016	benign	not specified	2018-04-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000404387	SCV000412483	benign	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000314041	SCV000412484	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	RCV000370968	SCV000412485	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	RCV000274147	SCV000412486	benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000079170	SCV000519600	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.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000314041	SCV001440600	benign	Malignant hyperthermia, susceptibility to, 1	2019-01-01	criteria provided, single submitter	clinical testing
Invitae	RCV001514061	SCV001721810	benign	RYR1-Related Disorders	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000404387	SCV002032915	benign	Central core myopathy	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001795070	SCV002032916	benign	King Denborough syndrome	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000370968	SCV002032917	benign	Congenital multicore myopathy with external ophthalmoplegia	2021-11-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000314041	SCV004358139	benign	Malignant hyperthermia, susceptibility to, 1	2018-03-05	criteria provided, single submitter	clinical testing
Leiden Muscular Dystrophy (RYR1)	RCV000119729	SCV000154636	not provided	not provided		no assertion provided	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000119729	SCV001553268	uncertain significance	not provided		no assertion criteria provided	clinical testing	Allele frequency is common in at least one population database (frequency: 46.669% 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.
Clinical Genetics, Academic Medical Center	RCV000079170	SCV001917396	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079170	SCV001953274	benign	not specified		no assertion criteria provided	clinical testing