ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4198A>G (p.Ser1400Gly)

gnomAD frequency: 0.01531  dbSNP: rs56229512
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 20
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000036743 SCV000050784 benign not specified 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036743 SCV000060398 benign not specified 2012-02-13 criteria provided, single submitter clinical testing Ser1400Gly in exon 32 of RYR2: This variant is classified as benign based on its high frequency in the general population (dbSNP rs56229512; NHLBI Exome Sequenc ing Project, http://evs.gs.washington.edu/EVS). G=157/A=6507 (EA chromosomes, E SP project)
PreventionGenetics, part of Exact Sciences RCV000036743 SCV000306056 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000244245 SCV000318829 benign Cardiovascular phenotype 2015-06-19 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 RCV001093763 SCV000356279 benign Catecholaminergic polymorphic ventricular tachycardia 1 2018-01-12 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 RCV000356250 SCV000356280 likely benign Arrhythmogenic right ventricular dysplasia 2 2018-01-12 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.
Invitae RCV001093763 SCV000554603 benign Catecholaminergic polymorphic ventricular tachycardia 1 2024-02-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756605 SCV000884471 benign not provided 2023-11-14 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000776018 SCV000910577 benign Cardiomyopathy 2018-03-15 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000756605 SCV000987473 benign not provided criteria provided, single submitter clinical testing
GeneDx RCV000756605 SCV001945577 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25925909, 33232181)
CeGaT Center for Human Genetics Tuebingen RCV000756605 SCV002497002 benign not provided 2024-07-01 criteria provided, single submitter clinical testing RYR2: BS1, BS2
Fulgent Genetics, Fulgent Genetics RCV002490497 SCV002802363 likely benign Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-12-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996280 SCV004817727 benign Catecholaminergic polymorphic ventricular tachycardia 2024-02-05 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000036743 SCV000280453 benign not specified 2015-02-10 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Ser1400Gly in the RYR2 gene. This variant is present in the 1000 Genomes browser with an overall allele frequency of 0.96% (http://browser.1000genomes.org/index.htm). This means that it is present in some 2% of individuals. In some ethnic subgroups the allele frequency is as high as 2-3%. This amino acid location is not conserved across paralog proteins RYR1-RYR3, suggesting that it is not important for channel function (https://cardiodb.org/Paralogue_Annotation/residue.php?gene=RYR2&position=1400). Yano et al. (2006) have reported that disease-causing variants in RYR2 cluster within 3 hotspot regions: the N-terminal domain (residues 77-433), the central domain (residues 2246-2534), and the C-terminal domain (residues 3778-4959). This variant falls outside of those 3 hotspots. No variation at nearby residues has been reported in HGMD in association with CPVT or ARVC (HGMD professional version as of January 17, 2014). ClinVar lists it as “Benign”, as submitted by Harvard’s Laboratory for Molecular Medicine. As of 2/2/2015 it has been reported in 14/1897 (0.74%) of African American individuals and 178/4126 (4.31%) of Caucasian individuals in the NHLBI Exome Sequencing Project dataset (for overall prevalence of 3.19%; http://evs.gs.washington.edu/EVS/), and two of the Caucasians with the variant were homozygous for it. The phenotype of the ESP individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. It is listed in dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP) as rs56229512.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000756605 SCV001739734 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000036743 SCV001918840 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000036743 SCV001927283 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000036743 SCV001951913 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000036743 SCV001964368 benign not specified no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.