Submissions for variant NM_001035.3(RYR2):c.11880+13_11880+16del

gnomAD frequency: 0.01032  dbSNP: rs199562036

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154647	SCV000204322	benign	not specified	2013-05-30	criteria provided, single submitter	clinical testing	11880+13_11880+16delACTG in intron 88 of RYR2: This variant is not expected to h ave clinical significance because it is not located within the splice consensus sequence and has been identified in 1.6% (125/7922) of European American chromos omes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/).
GeneDx	RCV000154647	SCV000235019	benign	not specified	2013-12-06	criteria provided, single submitter	clinical testing	The variant is found in ARVC, CPVT, POSTMORTEM, ARRHYTHMIA, CARDIOMYOPATHY panel(s).
Illumina Laboratory Services, Illumina	RCV000405071	SCV000356441	likely benign	Catecholaminergic polymorphic ventricular tachycardia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307997	SCV000356442	likely benign	Arrhythmogenic right ventricular cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154647	SCV001360982	benign	not specified	2019-08-26	criteria provided, single submitter	clinical testing	Variant summary: RYR2 c.11880+13_11880+16delACTG alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. The variant allele was found at a frequency of 0.011 in 248142 control chromosomes in the gnomAD database, including 25 homozygotes. The observed variant frequency is approximately 443 fold of the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001701532	SCV001473798	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Invitae	RCV002516105	SCV002414632	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336318	SCV002635702	benign	Cardiovascular phenotype	2014-12-08	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genetics, Academic Medical Center	RCV000154647	SCV001925692	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701532	SCV001931255	likely benign	not provided		no assertion criteria provided	clinical testing