Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001231418 | SCV001403938 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2022-05-21 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 731 of the JUP protein (p.Asp731Asn). This variant is present in population databases (rs782647137, gnomAD 0.006%). This missense change has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 25445213). ClinVar contains an entry for this variant (Variation ID: 958279). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. |
Ambry Genetics | RCV002429986 | SCV002728639 | uncertain significance | Cardiovascular phenotype | 2021-12-30 | criteria provided, single submitter | clinical testing | The p.D731N variant (also known as c.2191G>A), located in coding exon 13 of the JUP gene, results from a G to A substitution at nucleotide position 2191. The aspartic acid at codon 731 is replaced by asparagine, 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 alteration remains unclear. |