Submissions for variant NM_000540.3(RYR1):c.2505del (p.Pro836fs)

dbSNP: rs797045932

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000193833	SCV000248769	pathogenic	Myopathy	2015-07-17	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000318183	SCV000333573	pathogenic	not provided	2015-08-24	criteria provided, single submitter	clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV001249639	SCV001423606	pathogenic	Central core myopathy; Congenital multicore myopathy with external ophthalmoplegia	2017-05-10	criteria provided, single submitter	clinical testing	[ACMG/AMP: PVS1, PM2, PP5] This alteration is a null variant in a gene where LOF is a known mechanism of disease [PVS1], is absent from or rarely observed in large-scale population databases [PM2], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].
Labcorp Genetics (formerly Invitae), Labcorp	RCV001380374	SCV001578410	pathogenic	RYR1-related disorder	2024-03-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro836Leufs*48) in the RYR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 23919265, 25960145, 28818389, 30611313). This variant is present in population databases (rs797045932, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 212099). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000318183	SCV001803819	pathogenic	not provided	2025-01-05	criteria provided, single submitter	clinical testing	Identified in an individual from a large study of pediatric patients undergoing clinical exome sequencing and in an individual with myopathy, however detailed clinical information was not provided for either individual (PMID: 34691145, 32371413); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 38136118, 32371413, 39409197, 34691145)
Revvity Omics, Revvity	RCV000318183	SCV002019950	pathogenic	not provided	2020-10-02	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV003313945	SCV004014010	likely pathogenic	Congenital multicore myopathy with external ophthalmoplegia	2023-04-26	criteria provided, single submitter	clinical testing	PM2, PM3, PP2, PP3, PP5