ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4828C>T (p.Arg1610Ter) (rs794728738)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182728 SCV000235112 uncertain significance not provided 2018-01-17 criteria provided, single submitter clinical testing p.Arg1610Stop (CGA>TGA): c.4828 C>T in exon 36 of the RYR2 gene (NM_001035.2). The R1610X variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. R1610X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. However, the majority of disease-causing mutations in the RYR2 gene are either missense changes or small in-frame deletions/duplications that alter calcium release from the sarcoplasmic reticulum (SR). Similarly, the published in-frame deletion of exon three is predicted to decrease the threshold for termination of calcium release from the SR and thus increase the cytosolic calcium transient (Tang Y et al., 2012). Haploinsufficiency for RYR2 has not been definitively shown to cause cardiomyopathy in humans. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. Approximately 50% of patients with autosomal dominant CPVT have been reported to have a mutation in the RYR2 gene, while mutations in the RYR2 gene associated with ARVC are rare (McNally E et al., 2009; Napolitano C et al., 2012). The variant is found in CARDIOMYOPATHY panel(s).

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