ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.794G>A (p.Arg265His)

gnomAD frequency: 0.00001  dbSNP: rs782440692
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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 RCV001853126 SCV002252940 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-05-16 criteria provided, single submitter clinical testing 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. 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"). ClinVar contains an entry for this variant (Variation ID: 212751). This missense change has been observed in individual(s) with clinical features of Naxos disease (PMID: 21668431). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs782440692, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 265 of the JUP protein (p.Arg265His).
Ambry Genetics RCV002415828 SCV002677985 uncertain significance Cardiovascular phenotype 2023-09-28 criteria provided, single submitter clinical testing The p.R265H variant (also known as c.794G>A), located in coding exon 4 of the JUP gene, results from a G to A substitution at nucleotide position 794. The arginine at codon 265 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported as homozygous in two affected family members with arrhythmogenic right ventricular cardiomyopathy, alopecia, and palmoplantar keratoderma (Erken H et al. Br J Dermatol, 2011 Oct;165:917-21). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001853126 SCV002793527 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-11-02 criteria provided, single submitter clinical testing
OMIM RCV000194635 SCV000249577 pathogenic Naxos disease 2011-10-01 no assertion criteria provided literature only

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