Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002392004 | SCV002702766 | uncertain significance | Cardiovascular phenotype | 2018-07-06 | criteria provided, single submitter | clinical testing | The p.R477C variant (also known as c.1429C>T), located in coding exon 7 of the JUP gene, results from a C to T substitution at nucleotide position 1429. The arginine at codon 477 is replaced by cysteine, an amino acid with highly dissimilar properties. 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. |
| Labcorp Genetics |
RCV003095146 | SCV003032514 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2024-03-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 477 of the JUP protein (p.Arg477Cys). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 1772442). 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 disruptive. 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. |