Submissions for variant NM_001035.3(RYR2):c.13656T>C (p.His4552=)

gnomAD frequency: 0.00001  dbSNP: rs397516512

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036682	SCV000060337	likely benign	not specified	2012-06-26	criteria provided, single submitter	clinical testing	His4552His in exon 94 of RYR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. His4552His in exon 94 of RYR2 (allele frequ ency = n/a)
Ambry Genetics	RCV000252634	SCV000320617	likely benign	Cardiovascular phenotype	2020-01-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV001093791	SCV000356469	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	RCV000274155	SCV000356470	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769814	SCV000901240	likely benign	Cardiomyopathy	2016-06-26	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769814	SCV000904485	benign	Cardiomyopathy	2018-10-16	criteria provided, single submitter	clinical testing
Invitae	RCV001093791	SCV001009496	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2023-12-30	criteria provided, single submitter	clinical testing