Submissions for variant NM_001035.3(RYR2):c.9085A>G (p.Ile3029Val)

gnomAD frequency: 0.00002  dbSNP: rs370141970

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182773	SCV000235159	uncertain significance	not provided	2013-01-16	criteria provided, single submitter	clinical testing	p.Ile3029Val (ATT>GTT): c.9085 A>G in exon 64 of the RYR2 gene (NM_001035.2). The Ile3029Val variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ile3029Val results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved across species. The Ile3029Val variant was not observed with any significant frequency in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. However, in silico analysis predicts Ile3029Val is benign to the protein structure/function. Also, no mutations in nearby codons have been reported in association with CPVT, and Ile3029Val does not occur in one of the mutation hotspot regions of the RYR2 gene (Medeiros-Domingo A et al., 2009). We cannot definitively determine if Ile3029Val is a disease-causing mutation or a rare benign variant. The variant is found in CPVT panel(s).
Illumina Laboratory Services, Illumina	RCV000393089	SCV000356375	uncertain significance	Catecholaminergic polymorphic ventricular tachycardia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000314238	SCV000356376	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV002517797	SCV000760630	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001192120	SCV001360099	likely benign	Cardiomyopathy	2018-11-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003165392	SCV003858426	uncertain significance	Cardiovascular phenotype	2023-01-17	criteria provided, single submitter	clinical testing	The p.I3029V variant (also known as c.9085A>G), located in coding exon 64 of the RYR2 gene, results from an A to G substitution at nucleotide position 9085. The isoleucine at codon 3029 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.