Submissions for variant NM_000540.3(RYR1):c.9690G>A (p.Leu3230=)

gnomAD frequency: 0.05835  dbSNP: rs2304151

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079186	SCV000111055	benign	not specified	2013-07-31	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000079186	SCV000194882	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079186	SCV000305081	benign	not specified	2018-03-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000331165	SCV000412676	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	RCV000367176	SCV000412677	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	RCV000272601	SCV000412678	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	RCV000327649	SCV000412679	benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000079186	SCV000519833	benign	not specified	2016-01-29	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000079186	SCV000711709	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Leu3230Leu in exon 66 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 6.6% (571/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2304151).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001521655	SCV001731033	benign	RYR1-related disorder	2025-02-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000119773	SCV002049479	benign	not provided	2023-11-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000367176	SCV004358174	benign	Malignant hyperthermia, susceptibility to, 1	2019-03-29	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000119773	SCV005310860	benign	not provided		criteria provided, single submitter	not provided
Leiden Muscular Dystrophy (RYR1)	RCV000119773	SCV000154680	not provided	not provided		no assertion provided	not provided
Clinical Genetics, Academic Medical Center	RCV000079186	SCV001918093	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079186	SCV001954862	benign	not specified		no assertion criteria provided	clinical testing