ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13566C>T (p.Val4522=) (rs57360419)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036680 SCV000060335 benign not specified 2012-04-18 criteria provided, single submitter clinical testing Val4522Val in Exon 94 of RYR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and it has been identified in 1.0% (31/3128) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs57360419).
Invitae RCV001082867 SCV000285699 benign Catecholaminergic polymorphic ventricular tachycardia 2020-12-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000243868 SCV000319121 benign Cardiovascular phenotype 2015-07-28 criteria provided, single submitter clinical testing This alteration is classified as 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588704 SCV000697608 benign not provided 2017-03-13 criteria provided, single submitter clinical testing Variant summary: The RYR2 c.13566C>T (p.Val4522Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 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 85/38144 control chromosomes (2 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.02059 (81/3934). This frequency is about 374 times the estimated maximal expected allele frequency of a pathogenic RYR2 variant (0.000055), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. 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 nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Color Health, Inc RCV000777799 SCV000913791 benign Cardiomyopathy 2018-04-26 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287536 SCV001474235 likely benign none provided 2020-01-16 criteria provided, single submitter clinical testing
Clinical Genetics,Academic Medical Center RCV000036680 SCV001919107 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000036680 SCV001931765 benign not specified no assertion criteria provided clinical testing

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