ClinVar Miner

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

gnomAD frequency: 0.00004  dbSNP: rs200690479
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000171956 SCV000050948 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham 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; 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.
Invitae RCV000559192 SCV000645732 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 702 of the JUP protein (p.Arg702His). This variant is present in population databases (rs200690479, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with JUP-related conditions. ClinVar contains an entry for this variant (Variation ID: 178849). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV000619443 SCV000737685 uncertain significance Cardiovascular phenotype 2016-08-16 criteria provided, single submitter clinical testing The p.R702H variant (also known as c.2105G>A), located in coding exon 13 of the JUP gene, results from a G to A substitution at nucleotide position 2105. The arginine at codon 702 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This variant was previously reported in the SNPDatabase as rs200690479. Based on data from ExAC, the A allele has an overall frequency of <0.01% (6/104582). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
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
GeneDx RCV000171956 SCV001758212 uncertain significance not provided 2019-10-31 criteria provided, single submitter clinical testing Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 178849; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23861362)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798512 SCV002043155 uncertain significance Cardiomyopathy 2023-03-16 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000559192 SCV002792730 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-10-20 criteria provided, single submitter clinical testing

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