Submissions for variant NM_000540.3(RYR1):c.7500G>A (p.Ala2500=)

gnomAD frequency: 0.09736  dbSNP: rs2228072

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079165	SCV000111034	benign	not specified	2014-07-14	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000079165	SCV000194857	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000079165	SCV000269781	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Ala2500Ala in exon 47 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 12.0% (527/4406) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2228072).
PreventionGenetics, part of Exact Sciences	RCV000079165	SCV000305005	benign	not specified	2018-04-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000349039	SCV000412439	benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000403681	SCV000412440	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	RCV000300125	SCV000412441	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	RCV000357373	SCV000412442	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.
GeneDx	RCV000079165	SCV000519802	benign	not specified	2016-02-08	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	RCV001516954	SCV001725331	benign	RYR1-related disorder	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000403681	SCV002032905	benign	Central core myopathy	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001795067	SCV002032906	benign	King Denborough syndrome	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000357373	SCV002032908	benign	Congenital multicore myopathy with external ophthalmoplegia	2021-11-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000300125	SCV004358132	benign	Malignant hyperthermia, susceptibility to, 1	2019-03-29	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004716925	SCV005308640	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000079165	SCV001921009	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079165	SCV001951401	benign	not specified		no assertion criteria provided	clinical testing