Submissions for variant NM_000540.3(RYR1):c.8118T>C (p.Ile2706=)

gnomAD frequency: 0.33086  dbSNP: rs2960340

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079175	SCV000111044	benign	not specified	2014-06-06	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000079175	SCV000194869	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000079175	SCV000269788	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Ile2706Ile in exon 51 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 45.8% (2016/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2960340).
PreventionGenetics, part of Exact Sciences	RCV000079175	SCV000305040	benign	not specified	2018-04-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000405618	SCV000412543	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	RCV000310752	SCV000412544	benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000346944	SCV000412545	benign	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000406007	SCV000412546	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	RCV000079175	SCV000519602	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001514064	SCV001721813	benign	RYR1-related disorder	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000346944	SCV002032932	benign	Central core myopathy	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001795073	SCV002032933	benign	King Denborough syndrome	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000406007	SCV002032934	benign	Congenital multicore myopathy with external ophthalmoplegia	2021-11-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498391	SCV002812385	benign	Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome	2021-10-08	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000405618	SCV004358146	benign	Malignant hyperthermia, susceptibility to, 1	2019-03-29	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000119738	SCV005310829	benign	not provided		criteria provided, single submitter	not provided
Leiden Muscular Dystrophy (RYR1)	RCV000119738	SCV000154645	not provided	not provided		no assertion provided	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000119738	SCV001552721	uncertain significance	not provided		no assertion criteria provided	clinical testing	Allele frequency is common in at least one population database (frequency: 47.003% 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	RCV000079175	SCV001918471	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079175	SCV001956172	benign	not specified		no assertion criteria provided	clinical testing