Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000154729 | SCV000204409 | uncertain significance | not specified | 2013-08-09 | criteria provided, single submitter | clinical testing | The Arg177Gln variant in JUP has not been reported in individuals with cardiomyo pathy, but has been identified in 2/8600 of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Computation al analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhe n2, and SIFT) suggest that the Arg177Gln variant may not impact the protein, tho ugh this information is not predictive enough to rule out pathogenicity. Additio nal information is needed to fully assess the clinical significance of the Arg17 7Gln variant. |
Ambry Genetics | RCV000621366 | SCV000738210 | likely benign | Cardiovascular phenotype | 2021-11-18 | 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. |
Labcorp Genetics |
RCV000702831 | SCV000831702 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2024-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 177 of the JUP protein (p.Arg177Gln). This variant is present in population databases (rs371481933, gnomAD 0.006%). This missense change has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 178044). 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. |
Gene |
RCV002243826 | SCV002513133 | uncertain significance | not provided | 2022-04-25 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 31402444) |
Fulgent Genetics, |
RCV000702831 | SCV002814385 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2024-05-14 | criteria provided, single submitter | clinical testing |