Submissions for variant NM_000540.3(RYR1):c.8360C>G (p.Thr2787Ser)

gnomAD frequency: 0.00291  dbSNP: rs35180584

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen	RCV001802881	SCV002047633	benign	Malignant hyperthermia of anesthesia	2021-12-22	reviewed by expert panel	curation	This pathogenicity assessment is relevant only for malignant hyperthermia susceptibility (MHS) inherited in an autosomal dominant pattern. Variants in RYR1 can also cause other myopathies inherited in an autosomal dominant pattern or in an autosomal recessive pattern. Some of these disorders may predispose individuals to malignant hyperthermia. RYR1 variants may also contribute to a malignant hyperthermia reaction in combination with other genetic and non-genetic factors and the clinician needs to consider such factors in making management decisions. This sequence variant predicts a substitution of threonine with serine at codon 2787 of the RYR1 protein, p.(Thr2787Ser). The maximum allele frequency for this variant among the six major gnomAD populations is AFR: 0.029867, which is considered to be too common for a pathogenic variant causing autosomal dominantly inherited MHS, BA1. This variant has been classified as Benign. Criteria implemented: BA1.
Genetic Services Laboratory, University of Chicago	RCV000147446	SCV000194873	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202878	SCV000257715	benign	Malignant hypothermia	2015-06-26	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000209984	SCV000265729	benign	Malignant hyperthermia, susceptibility to, 1	2013-07-01	criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000147446	SCV000333096	benign	not specified	2015-07-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000392959	SCV000412563	likely benign	Central core myopathy	2018-02-09	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000209984	SCV000412564	likely benign	Malignant hyperthermia, susceptibility to, 1	2018-02-09	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000335435	SCV000412565	likely benign	Congenital multicore myopathy with external ophthalmoplegia	2018-02-09	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000403812	SCV000412566	likely benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079361	SCV000660062	benign	RYR1-related disorder	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000147446	SCV000730604	benign	not specified	2017-04-17	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.
Athena Diagnostics	RCV000119746	SCV001145296	benign	not provided	2018-12-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000119746	SCV002498466	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	RYR1: BS1, BS2
Fulgent Genetics, Fulgent Genetics	RCV002498553	SCV002800437	benign	Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome	2022-05-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000119746	SCV003799804	benign	not provided	2023-10-14	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000209984	SCV004358153	benign	Malignant hyperthermia, susceptibility to, 1	2019-03-29	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000119746	SCV005310832	benign	not provided		criteria provided, single submitter	not provided
Leiden Muscular Dystrophy (RYR1)	RCV000119746	SCV000154653	not provided	not provided		no assertion provided	not provided
PreventionGenetics, part of Exact Sciences	RCV001079361	SCV000305045	benign	RYR1-related disorder	2019-05-29	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000119746	SCV001800004	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000147446	SCV001952377	benign	not specified		no assertion criteria provided	clinical testing