ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1331G>A (p.Arg444His) (rs369507567)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533569 SCV000645724 uncertain significance Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2017-04-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 444 of the JUP protein (p.Arg444His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs369507567, ExAC 0.01%) but has not been reported in the literature in individuals with a JUP-related disease. ClinVar contains an entry for this variant (Variation ID: 45833). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039062 SCV000062740 uncertain significance not specified 2012-11-28 criteria provided, single submitter clinical testing The Arg444His variant in JUP has not been reported in the literature nor previou sly identified by our laboratory but has been identified in 1/8600 European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS/). Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ar g444His variant may not impact the protein, though this information is not predi ctive enough to rule out pathogenicity. In summary, additional studies are neede d to fully assess its clinical significance.

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