ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.286G>A (p.Glu96Lys)

gnomAD frequency: 0.00002  dbSNP: rs191683892
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183483 SCV000235943 uncertain significance not provided 2014-02-06 criteria provided, single submitter clinical testing p.Glu96Lys (GAG>AAG): c.286 G>A in exon 3 of the JUP gene (NM_002230.2)The E96K variant in the JUP gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The E96K variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The E96 residue is mostly conserved across species. In silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. The E96K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the E96K variant was identified with a frequency of 0.8%, 1/118 alleles, in a sub-population of individuals of Mexican ancestry per the 1000 Genomes Project database. The variant is found in ARVC panel(s).
Invitae RCV001047557 SCV001211522 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2023-11-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 96 of the JUP protein (p.Glu96Lys). This variant is present in population databases (rs191683892, 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: 201809). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192707 SCV001360999 uncertain significance not specified 2019-04-29 criteria provided, single submitter clinical testing Variant summary: JUP c.286G>A (p.Glu96Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.3e-05 in 262198 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.286G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798638 SCV002043156 uncertain significance Cardiomyopathy 2019-11-20 criteria provided, single submitter clinical testing

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