Submissions for variant NM_001035.3(RYR2):c.1477-11dup

dbSNP: rs397516518

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036702	SCV000060357	likely benign	not specified	2012-04-05	criteria provided, single submitter	clinical testing	1477-11_1477-10insT in intron 15 of RYR2: This variant is not expected to have c linical significance because it is located outside the conserved +/- 1, 2 region of the splicing consensus sequence and is part of a polyT stretch. 1477-11_147 7-10insT in intron 15 of RYR2 (allele frequency = n/a)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000036702	SCV001362245	benign	not specified	2019-08-19	criteria provided, single submitter	clinical testing	Variant summary: RYR2 c.1477-11dupT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.4 in 170484 control chromosomes in the gnomAD database, including 3845 homozygotes. The observed variant frequency is approximately 16047-folds over 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001530809	SCV001745709	benign	not provided	2015-04-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798108	SCV002042902	benign	Cardiomyopathy	2020-10-16	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000036702	SCV001741322	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000036702	SCV001959122	benign	not specified		no assertion criteria provided	clinical testing