Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000687366 | SCV000814929 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2024-07-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 496 of the JUP protein (p.Pro496Thr). This variant is not present in population databases (gnomAD no frequency). 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: 567321). 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. |
Gene |
RCV001771937 | SCV001993506 | uncertain significance | not provided | 2019-05-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as a variant of uncertain significance by another clinical laboratory (ClinVar Variant ID# 567321; Landrum et al., 2016) |
Ambry Genetics | RCV002388205 | SCV002702641 | uncertain significance | Cardiovascular phenotype | 2022-09-09 | criteria provided, single submitter | clinical testing | The p.P496T variant (also known as c.1486C>A), located in coding exon 7 of the JUP gene, results from a C to A substitution at nucleotide position 1486. The proline at codon 496 is replaced by threonine, an amino acid with highly similar 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. |