Submissions for variant NM_000540.3(RYR1):c.9353C>T (p.Ala3118Val)

gnomAD frequency: 0.00188  dbSNP: rs2915960

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen	RCV000295514	SCV001816192	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 Valine at codon 3118 of the RYR1 protein, p.(Ala3118Val). The maximum allele frequency for this variant among the six major gnomAD populations is AFR: 0.0063, 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.
Illumina Laboratory Services, Illumina	RCV000387418	SCV000412640	likely benign	Central core myopathy	2019-08-14	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	RCV000295514	SCV000412641	likely benign	Malignant hyperthermia, susceptibility to, 1	2019-08-14	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	RCV000352587	SCV000412642	likely benign	Congenital multicore myopathy with external ophthalmoplegia	2019-08-14	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	RCV000372340	SCV000412643	likely benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085870	SCV000660087	likely benign	RYR1-related disorder	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000721736	SCV000731107	likely benign	not provided	2019-08-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000624697	SCV000741876	uncertain significance	Inborn genetic diseases	2016-10-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000721736	SCV000852866	likely benign	not provided	2016-06-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000721736	SCV004701942	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	RYR1: PP3, BS1