Submissions for variant NM_000540.3(RYR1):c.5628GGA[2] (p.Glu1878del)

dbSNP: rs371047178

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000333149	SCV000412281	likely benign	Malignant hyperthermia of anesthesia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000362205	SCV000412282	likely benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000270289	SCV000412283	likely benign	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000327677	SCV000412284	likely benign	Multiminicore myopathy	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000481398	SCV000569618	likely benign	not specified	2016-10-19	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.
Genetic Services Laboratory, University of Chicago	RCV000481398	SCV000596900	uncertain significance	not specified	2016-07-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000540470	SCV000659969	likely benign	RYR1-related disorder	2025-01-19	criteria provided, single submitter	clinical testing
Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS	RCV000270289	SCV000920385	likely pathogenic	Central core myopathy	2019-01-01	criteria provided, single submitter	research	The same individual also harbours another variant g.[38969101T>C] in the same gene along with this variant as compound heterozygote
Revvity Omics, Revvity	RCV003129835	SCV003814464	uncertain significance	not provided	2022-04-14	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV003129835	SCV004224627	uncertain significance	not provided	2023-01-12	criteria provided, single submitter	clinical testing	PM4
All of Us Research Program, National Institutes of Health	RCV003995867	SCV004820861	likely benign	Malignant hyperthermia, susceptibility to, 1	2024-09-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000481398	SCV005883824	likely benign	not specified	2024-12-03	criteria provided, single submitter	clinical testing	Variant summary: RYR1 c.5634_5636delGGA (p.Glu1878del) results in an in-frame deletion that is located within a Glu stretch, and shortens it by one amino acid. The variant allele was found at a frequency of 0.00045 in 248600 control chromosomes, predominantly at a frequency of 0.0016 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The variant, c.5634_5636delGGA, has been reported in the literature in a fetus with sonographic findings as suggesting arthrogryposis multiplex, however no supportive evidence for causality has been provided (Aggarwal_2019, Saini_2022). These reports do not provide unequivocal conclusions about association of the variant with Myopathy, RYR1-Associated. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31742715, 35587316). ClinVar contains an entry for this variant (Variation ID: 329041). Based on the evidence outlined above, the variant was classified as likely benign.
Color Diagnostics, LLC DBA Color Health	RCV003995867	SCV006064786	likely benign	Malignant hyperthermia, susceptibility to, 1	2022-05-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000540470	SCV004793534	likely benign	RYR1-related disorder	2022-09-07	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).