Submissions for variant NM_000540.3(RYR1):c.13502C>T (p.Pro4501Leu)

gnomAD frequency: 0.00601  dbSNP: rs73933023

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen	RCV000210000	SCV001816198	benign	Malignant hyperthermia, susceptibility to, 1	2021-03-16	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 Proline with Leucine at codon 4501 of the RYR1 protein, p.(Pro4501Leu). The maximum allele frequency for this variant among the six major gnomAD populations is AFR: 0.0181, 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.
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000210000	SCV000265747	likely benign	Malignant hyperthermia, susceptibility to, 1	2013-07-01	criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000243297	SCV000341640	benign	not specified	2016-06-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000262131	SCV000412967	likely benign	Neuromuscular disease, congenital, with uniform type 1 fiber	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000319074	SCV000412968	likely benign	Congenital multicore myopathy with external ophthalmoplegia	2018-05-15	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	RCV000210000	SCV000412969	likely benign	Malignant hyperthermia, susceptibility to, 1	2018-05-15	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	RCV000274979	SCV000412970	likely benign	Central core myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000427695	SCV000511128	likely benign	not provided	2016-09-13	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
GeneDx	RCV000427695	SCV000521248	benign	not provided	2018-03-27	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24195946, 28326467, 22995991, 21795085, 20981092, 19191329, 27884173, 28750945, 30611313)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082008	SCV000659819	benign	RYR1-related disorder	2024-01-30	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002500678	SCV002810568	likely benign	Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome	2021-07-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000427695	SCV002822561	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	RYR1: BS1, BS2
Color Diagnostics, LLC DBA Color Health	RCV000210000	SCV004358211	benign	Malignant hyperthermia, susceptibility to, 1	2022-08-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000427695	SCV005310894	benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV001082008	SCV000304821	benign	RYR1-related disorder	2019-06-19	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).