Submissions for variant NM_000540.3(RYR1):c.9186A>G (p.Pro3062=)

gnomAD frequency: 0.32394  dbSNP: rs2071089

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079184	SCV000111053	benign	not specified	2014-06-06	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000079184	SCV000194879	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000079184	SCV000269793	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Pro3062Pro in exon 62 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% (1882/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2071089).
PreventionGenetics, part of Exact Sciences	RCV000079184	SCV000305071	benign	not specified	2018-04-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000293902	SCV000412624	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	RCV000351185	SCV000412625	benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000406849	SCV000412626	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	RCV000297297	SCV000412627	benign	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000079184	SCV000519607	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.
Invitae	RCV001514069	SCV001721818	benign	RYR1-related disorder	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000297297	SCV002032975	benign	Central core myopathy	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001795081	SCV002032976	benign	King Denborough syndrome	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000406849	SCV002032977	benign	Congenital multicore myopathy with external ophthalmoplegia	2021-11-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000293902	SCV004358162	benign	Malignant hyperthermia, susceptibility to, 1	2019-03-29	criteria provided, single submitter	clinical testing
Leiden Muscular Dystrophy (RYR1)	RCV000119767	SCV000154674	not provided	not provided		no assertion provided	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000119767	SCV001554233	uncertain significance	not provided		no assertion criteria provided	clinical testing	Allele frequency is common in at least one population database (frequency: 45.77% 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	RCV000079184	SCV001918042	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079184	SCV001951222	benign	not specified		no assertion criteria provided	clinical testing