Submissions for variant NM_001035.2(RYR2):c.14091-11dup

dbSNP: rs35563566

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036690	SCV000060345	likely benign	not specified	2011-09-28	criteria provided, single submitter	clinical testing	14091-11_14091-10insT in intron 97 of RYR2: This variant is not expected to have clinical significance because it is located outside the conserved +/- 1, 2 regi on of the splicing consensus sequence and as part of a polyT stretch. This vari ant has been reported in dbSNP (rs72027983 & rs55683196) without frequency infor mation.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000036690	SCV000918176	benign	not specified	2018-01-12	criteria provided, single submitter	clinical testing	Variant summary: The RYR2 c.14091-11dupT variant involves the alteration of an intronic nucleotide in a poly-T stretch. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 10364/27792 control chromosomes (1716 homozygotes)in gnomAD at a frequency of 0.3729131, which is approximately 6780 times the estimated maximal expected allele frequency of a pathogenic RYR2 variant (0.000055), suggesting this variant is likely a benign polymorphism. In addition, one laboratory classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx	RCV001610317	SCV001842380	benign	not provided	2019-08-19	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798107	SCV002042898	benign	Cardiomyopathy	2020-09-30	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036690	SCV001923283	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000036690	SCV001963117	benign	not specified		no assertion criteria provided	clinical testing