Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001232198 | SCV001404744 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2023-06-09 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 958935). This variant has not been reported in the literature in individuals affected with JUP-related conditions. This variant is present in population databases (rs782261124, gnomAD 0.01%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 730 of the JUP protein (p.Ser730Asn). |
Gene |
RCV001760237 | SCV001989660 | uncertain significance | not provided | 2019-07-30 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
Ambry Genetics | RCV002429990 | SCV002728567 | likely benign | Cardiovascular phenotype | 2023-07-06 | 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. |
Prevention |
RCV004754708 | SCV005360548 | uncertain significance | JUP-related disorder | 2024-08-10 | no assertion criteria provided | clinical testing | The JUP c.2189G>A variant is predicted to result in the amino acid substitution p.Ser730Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% 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. |