ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.5001T>C (p.Leu1667=) (rs397516537)

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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 RCV000036759 SCV000060414 likely benign not specified 2012-10-08 criteria provided, single submitter clinical testing Leu1667Leu in exon 37 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. Leu1667Leu in exon 37 of RYR2 (allele freque ncy = n/a)
GeneDx RCV000036759 SCV000171414 benign not specified 2014-04-08 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000469222 SCV000554581 likely benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617438 SCV000736805 likely benign Cardiovascular phenotype 2017-04-04 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768772 SCV000900142 likely benign Cardiomyopathy 2016-11-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000036759 SCV000918165 benign not specified 2018-05-29 criteria provided, single submitter clinical testing Variant summary: RYR2 c.5001T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 6-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.5001T>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign." Based on the evidence outlined above, the variant was classified as benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001090709 SCV001246393 likely benign not provided 2019-12-01 criteria provided, single submitter clinical testing
Color RCV000768772 SCV001339615 likely benign Cardiomyopathy 2018-11-25 criteria provided, single submitter clinical testing

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