Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001811779 | SCV002050191 | uncertain significance | not provided | 2020-11-18 | criteria provided, single submitter | clinical testing | The JUP c.1113C>A; p.Asn371Lys variant (rs782009178), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on a single chromosome in the Genome Aggregation Database (1/251280 alleles), indicating it is not a common polymorphism. The asparagine at codon 371 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.679). Given the lack of clinical and functional data, the significance of the p.Asn371Lys variant is uncertain at this time. |
| Ambry Genetics | RCV003299011 | SCV003997551 | uncertain significance | Cardiovascular phenotype | 2023-03-22 | criteria provided, single submitter | clinical testing | The p.N371K variant (also known as c.1113C>A), located in coding exon 6 of the JUP gene, results from a C to A substitution at nucleotide position 1113. The asparagine at codon 371 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005213600 | SCV005854638 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2025-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 371 of the JUP protein (p.Asn371Lys). This variant is present in population databases (rs782009178, 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: 1330649). 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. |