Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000171960 | SCV000050950 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Gene |
RCV000171960 | SCV002588186 | uncertain significance | not provided | 2022-04-26 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function |
Ambry Genetics | RCV002372073 | SCV002686465 | uncertain significance | Cardiovascular phenotype | 2022-06-30 | criteria provided, single submitter | clinical testing | The p.A314G variant (also known as c.941C>G), located in coding exon 5 of the JUP gene, results from a C to G substitution at nucleotide position 941. The alanine at codon 314 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003765079 | SCV004606469 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 314 of the JUP protein (p.Ala314Gly). This variant is present in population databases (rs201214805, gnomAD 0.0009%). 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: 191673). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |