ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1130G>A (p.Arg377His)

gnomAD frequency: 0.00005  dbSNP: rs794729044
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000645201 SCV000766943 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-08-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 377 of the JUP protein (p.Arg377His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs200433530, ExAC 0.02%). This missense change has been observed in individual(s) with arrhythmogenic right ventricularcardiomyopathy (PMID: 25765472). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg377 amino acid residue in JUP. Other variant(s) that disrupt this residue have been observed in individuals with JUP-related conditions (PMID: 25765472), which suggests that this may be a clinically significant amino acid residue. 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.
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine RCV001251003 SCV001426404 uncertain significance Arrhythmogenic right ventricular dysplasia 12 criteria provided, single submitter research
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798639 SCV002043152 uncertain significance Cardiomyopathy 2020-03-17 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004754339 SCV005366598 uncertain significance JUP-related disorder 2024-07-10 no assertion criteria provided clinical testing The JUP c.1130G>A variant is predicted to result in the amino acid substitution p.Arg377His. This variant has been reported in an individual with arrhythmogenic right ventricular cardiomyopathy and a case of sudden infant death syndrome (Zhou et al. 2015. PubMed ID: 25765472; Köffer et al. 2020. PubMed ID: 32789579). This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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