Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000039062 | SCV000062740 | uncertain significance | not specified | 2012-11-28 | criteria provided, single submitter | clinical testing | The Arg444His variant in JUP has not been reported in the literature nor previou sly identified by our laboratory but has been identified in 1/8600 European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS/). Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ar g444His variant may not impact the protein, though this information is not predi ctive enough to rule out pathogenicity. In summary, additional studies are neede d to fully assess its clinical significance. |
| Labcorp Genetics |
RCV000533569 | SCV000645724 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2024-09-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 444 of the JUP protein (p.Arg444His). This variant is present in population databases (rs369507567, gnomAD 0.02%). 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: 45833). 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 tolerated. 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, |
RCV000533569 | SCV002790071 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2021-11-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003162344 | SCV003911576 | likely benign | Cardiovascular phenotype | 2022-11-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |