Submissions for variant NM_000540.3(RYR1):c.4055C>G (p.Ala1352Gly)

gnomAD frequency: 0.00685  dbSNP: rs112105381

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen	RCV000148802	SCV001816191	benign	Malignant hyperthermia, susceptibility to, 1	2021-03-17	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 Alanine with Glycine at codon 1352 of the RYR1 protein, p.(Ala1352Gly). The maximum allele frequency for this variant among the six major gnomAD populations is AFR: 0.0222, 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	RCV000147424	SCV000194829	benign	not specified	2021-12-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV001080909	SCV000304922	benign	RYR1-related disorder	2021-08-25	criteria provided, single submitter	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).
Illumina Laboratory Services, Illumina	RCV000148802	SCV000412096	benign	Malignant hyperthermia, susceptibility to, 1	2018-03-06	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.
Invitae	RCV001080909	SCV000659929	benign	RYR1-related disorder	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000721517	SCV000730603	benign	not provided	2020-01-20	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19807743, 19191329, 25735680, 22995991, 25637381, 21795085, 26332594, 25985138)
Illumina Laboratory Services, Illumina	RCV001126223	SCV001285387	benign	Congenital multicore myopathy with external ophthalmoplegia	2018-03-06	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	RCV001126224	SCV001285388	benign	Central core myopathy	2018-03-06	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.
CeGaT Center for Human Genetics Tuebingen	RCV000721517	SCV004033661	benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	RYR1: PM5, BP4, BS1, BS2
Color Diagnostics, LLC DBA Color Health	RCV000148802	SCV004358064	benign	Malignant hyperthermia, susceptibility to, 1	2022-05-04	criteria provided, single submitter	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148802	SCV000190540	likely benign	Malignant hyperthermia, susceptibility to, 1	2014-06-01	no assertion criteria provided	research