ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.2402G>T (p.Arg801Leu) (rs371157868)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036718 SCV000060373 uncertain significance not specified 2015-04-09 criteria provided, single submitter clinical testing The p.Arg801Leu variant in RYR2 has been identified by our laboratory in 1 Cauca sian adolescent with HCM. The variant has also been identified in 3/29120 Europe an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti; dbSNP rs371157868). Computational prediction tools and conservation an alysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical s ignificance of the p.Arg801Leu variant is uncertain.
GeneDx RCV000766710 SCV000235078 uncertain significance not provided 2018-11-21 criteria provided, single submitter clinical testing p.Arg801Leu (R801L) CGC>CTC: c.2402 G>T in exon 22 of the RYR2 gene (NM_001035.2). The Arg801Leu variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg801Leu results in a non-conservative amino acid substitution of positively-charged Arginine with a nonpolar Leucine at a position that is conserved across species. In silico analysis predicts Arg801Leu is damaging to the protein structure/function. However, Arg801Leu does not occur in any of the hotspot regions of the RYR2 gene, and there have been no nearby mutations reported in association with arrhythmia, indicating this region of the protein may be tolerant of change. Arg801Leu was not present in the 1000 Genomes database, but the NHLBI ESP Exome Variant Server reports Arg801Leu was observed in 3/8218 alleles (0.03%) from individuals of European background. With the clinical and molecular information available at this time, we cannot definitively determine if Arg801Leu is a disease-causing mutation or a rare benign variant. The variant is found in CPVT,CARDIOMYOPATHY panel(s).
CSER_CC_NCGL; University of Washington Medical Center RCV000590875 SCV000700094 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2016-10-01 criteria provided, single submitter research Found in patient having exome sequencing for an unrelated indication. No known history of arrhythmogenic right ventricular dysplasia. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review.
Ambry Genetics RCV000621156 SCV000737829 uncertain significance Cardiovascular phenotype 2016-12-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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