Submissions for variant NM_001035.3(RYR2):c.4605G>A (p.Pro1535=)

gnomAD frequency: 0.00117  dbSNP: rs201916326

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036748	SCV000060403	benign	not specified	2015-12-04	criteria provided, single submitter	clinical testing	p.Pro1535Pro in exon 35 of RYR2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 1.6% (257/15602) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs201916326).
Invitae	RCV001093863	SCV000285728	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000244683	SCV000318331	benign	Cardiovascular phenotype	2016-10-03	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.
Illumina Laboratory Services, Illumina	RCV001093863	SCV000356287	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000345910	SCV000356288	likely benign	Arrhythmogenic right ventricular dysplasia 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000776059	SCV000910694	benign	Cardiomyopathy	2018-03-08	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000776059	SCV001333891	benign	Cardiomyopathy	2017-11-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001529303	SCV001886644	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001529303	SCV002544382	benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	RYR2: BP4, BP7, BS1, BS2
All of Us Research Program, National Institutes of Health	RCV003996282	SCV004818322	benign	Catecholaminergic polymorphic ventricular tachycardia	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529303	SCV001742523	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036748	SCV001920486	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000036748	SCV001926453	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529303	SCV001971926	likely benign	not provided		no assertion criteria provided	clinical testing