Submissions for variant NM_000540.3(RYR1):c.9713A>G (p.Glu3238Gly)

gnomAD frequency: 0.00016  dbSNP: rs200950673

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000725266	SCV000234972	uncertain significance	not provided	2020-11-03	criteria provided, single submitter	clinical testing	Reported in an individual with late-onset myopathy in the published literature (Loseth et al., 2013); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25637381, 23329375, 25747005, 23558838)
Eurofins Ntd Llc (ga)	RCV000725266	SCV000335493	uncertain significance	not provided	2015-09-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000382036	SCV000412680	likely benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000287628	SCV000412681	likely benign	Malignant hyperthermia of anesthesia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000323995	SCV000412682	likely benign	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000378617	SCV000412683	likely benign	Multiminicore myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000281816	SCV000540244	uncertain significance	not specified	2017-01-25	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant has been reported in one patient with axial myopathy and one who is malignant hyperthermia susceptible as determined by the Caffeine contracture test. The variant has a Max MAF of 0.1% in ExAC (19 South Asian alleles) and 0.1% in gnomAD (35 South Asian alleles). Frequency is too high for disease. It is classified with 1 star in ClinVar as VUS by GeneDx and as Likely benign by CSER_CC_NCGL.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084344	SCV000660097	likely benign	RYR1-related disorder	2024-01-30	criteria provided, single submitter	clinical testing
Mendelics	RCV000990203	SCV001141067	benign	Malignant hyperthermia, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000281816	SCV002766078	likely benign	not specified	2024-03-29	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000725266	SCV003827505	uncertain significance	not provided	2022-08-04	criteria provided, single submitter	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148800	SCV000190538	likely benign	Axial myopathy, late-onset	2014-06-01	no assertion criteria provided	research