Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000532535 | SCV000645727 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2024-09-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 572 of the JUP protein (p.Arg572Trp). This variant is present in population databases (rs559297418, gnomAD 0.007%). 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: 468746). 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. |
Fulgent Genetics, |
RCV000532535 | SCV002793286 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2021-11-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004992344 | SCV005601726 | uncertain significance | Cardiovascular phenotype | 2024-09-12 | criteria provided, single submitter | clinical testing | The p.R572W variant (also known as c.1714C>T), located in coding exon 9 of the JUP gene, results from a C to T substitution at nucleotide position 1714. The arginine at codon 572 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in cardiomyopathy cohorts in affected individuals and the control population (Bao J et al. Circ Cardiovasc Genet, 2013 Dec;6:552-6; Kühnisch J et al. Clin Genet, 2019 Dec;96:549-559). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Prevention |
RCV004754466 | SCV005360772 | uncertain significance | JUP-related disorder | 2024-08-13 | no assertion criteria provided | clinical testing | The JUP c.1714C>T variant is predicted to result in the amino acid substitution p.Arg572Trp. This variant has been reported in both control and affected individuals in a case-control study of arrhythmogenic right ventricular cardiomyopathy. This variant was not considered to be a primary cause of disease (Table S2, Bao et al. 2013. PubMed ID: 24125834). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |