ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.257G>A (p.Arg86Gln) (rs782341732)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425824 SCV000535399 uncertain significance not provided 2016-12-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the JUP gene. The R86Q variant has not been published as apathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed inapproximately 6,500 individuals of European and African American ancestry in the NHLBI Exome SequencingProject, indicating it is not a common benign variant in these populations. The R86Q variant is a semi-conservativeamino acid substitution, which may impact secondary protein structure as these residues differ in some properties.Moreover, this substitution occurs at a position that is conserved across species, and in silico analysis predicts thisvariant is probably damaging to the protein structure/function. Nonetheless, this variant lacks observation in asignificant number of affected individuals, segregation data, and functional evidence, all of which would further clarifypathogenicity.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.This result cannot be interpreted for diagnosis or used for family member screening at this time
Invitae RCV000645206 SCV000766948 uncertain significance Naxos disease; Arrhythmogenic right ventricular cardiomyopathy, type 12 2017-11-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 86 of the JUP protein (p.Arg86Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with JUP-related disease. ClinVar contains an entry for this variant (Variation ID: 392175). 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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