ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.530G>A (p.Arg177Gln) (rs371481933)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154729 SCV000204409 uncertain significance not specified 2013-08-09 criteria provided, single submitter clinical testing The Arg177Gln variant in JUP has not been reported in individuals with cardiomyo pathy, but has been identified in 2/8600 of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Computation al analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhe n2, and SIFT) suggest that the Arg177Gln variant may not impact the protein, tho ugh this information is not predictive enough to rule out pathogenicity. Additio nal information is needed to fully assess the clinical significance of the Arg17 7Gln variant.
Ambry Genetics RCV000621366 SCV000738210 uncertain significance Cardiovascular phenotype 2017-10-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000702831 SCV000831702 uncertain significance Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 177 of the JUP protein (p.Arg177Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs371481933, ExAC 0.005%). This variant has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy (ARVC) (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 178044). 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.

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