Submissions for variant NM_000540.3(RYR1):c.7260C>T (p.His2420=)

gnomAD frequency: 0.03031  dbSNP: rs12973632

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000147438	SCV000194853	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000147438	SCV000203456	benign	not specified	2014-02-17	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000147438	SCV000269780	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.His2420His in exon 45 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 3.3% (287/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12973632).
PreventionGenetics, part of Exact Sciences	RCV000147438	SCV000305001	benign	not specified	2018-04-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000287054	SCV000412415	benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000339275	SCV000412416	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	RCV000403377	SCV000412417	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	RCV000290153	SCV000412418	benign	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000147438	SCV000515934	benign	not specified	2015-06-22	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	RCV000527440	SCV000660022	benign	RYR1-Related Disorders	2024-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000119692	SCV001145295	benign	not provided	2019-06-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483210	SCV002803151	benign	Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome	2021-08-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000339275	SCV004358122	benign	Malignant hyperthermia, susceptibility to, 1	2019-03-29	criteria provided, single submitter	clinical testing
Leiden Muscular Dystrophy (RYR1)	RCV000119692	SCV000154599	not provided	not provided		no assertion provided	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000119692	SCV001797779	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000147438	SCV001921120	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000147438	SCV001958509	benign	not specified		no assertion criteria provided	clinical testing