Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000243320 | SCV000320558 | uncertain significance | Cardiovascular phenotype | 2023-02-23 | criteria provided, single submitter | clinical testing | The p.A445P variant (also known as c.1333G>C), located in coding exon 7 of the JUP gene, results from a G to C substitution at nucleotide position 1333. The alanine at codon 445 is replaced by proline, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| ARUP Laboratories, |
RCV000506902 | SCV000604054 | uncertain significance | not specified | 2016-12-21 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001230046 | SCV001402513 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2023-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 445 of the JUP protein (p.Ala445Pro). This variant is present in population databases (rs782465430, gnomAD 0.002%). 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: 264551). 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. |