ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.5543C>T (p.Pro1848Leu)

dbSNP: rs397516543
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036767 SCV000060422 uncertain significance not specified 2012-09-21 criteria provided, single submitter clinical testing The Pro1848Leu variant in RYR2 has not been reported in the literature and has n ot been identified in large and broad European American and African American pop ulations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS ). This low frequency is consistent with a disease causing role but insufficient to establish this with confidence. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Pro1848Leu variant may impact the protein, though this information is not predic tive enough to determine pathogenicity. Additional studies are needed to fully a ssess its clinical significance.
All of Us Research Program, National Institutes of Health RCV003996291 SCV004838336 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 1848 of the RYR2 protein. Computational prediction tool indicates that this variant may have deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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