ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.2105G>A (p.Arg702His) (rs200690479)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619443 SCV000737685 uncertain significance Cardiovascular phenotype 2016-08-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171956 SCV000050948 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV000559192 SCV000645732 uncertain significance Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2017-08-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 702 of the JUP protein (p.Arg702His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs200690479, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with JUP-related disease. ClinVar contains an entry for this variant (Variation ID: 178849). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000155621 SCV000205329 uncertain significance not specified 2015-05-16 criteria provided, single submitter clinical testing The p.Arg702His variant in JUP has been identified by our laboratory in 1 Caucas ian individual with CPVT. However, this individual carried a pathogenic variant in RYR2, and the p.Arg702His variant was also found in an apparently unaffected member of the same family. This variant has also been identified in 8/66036 Euro pean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org; dbSNP rs200690479). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg702His variant is uncertain.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000622902 SCV000740581 uncertain significance Left ventricular noncompaction 2017-04-04 criteria provided, single submitter clinical testing

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