Submissions for variant NM_001035.3(RYR2):c.11557+19C>T

gnomAD frequency: 0.01994  dbSNP: rs113408406

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000180424	SCV000053079	benign	not specified	2018-01-12	criteria provided, single submitter	clinical testing	Variant summary: The RYR2 c.11557+19C>T variant involves the alteration of a non-conserved intronic nucleotide. 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 3274/177350 control chromosomes (53 homozygotes) at a frequency of 0.0184607, which is approximately 336 times the estimated maximal expected allele frequency of a pathogenic RYR2 variant (0.000055), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as 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.
Eurofins Ntd Llc (ga)	RCV000180424	SCV000232855	benign	not specified	2014-09-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000180424	SCV000306026	benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001528341	SCV001157495	benign	not provided	2023-11-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001528341	SCV001849427	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513260	SCV002375392	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-02-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001528341	SCV005280797	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528341	SCV001739934	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000180424	SCV001924535	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000180424	SCV001927940	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000180424	SCV001956406	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000180424	SCV001969594	benign	not specified		no assertion criteria provided	clinical testing