Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003380178 | SCV004096310 | uncertain significance | Cardiovascular phenotype | 2023-07-31 | criteria provided, single submitter | clinical testing | The p.K124* variant (also known as c.370A>T), located in coding exon 2 of the JUP gene, results from an A to T substitution at nucleotide position 370. This changes the amino acid from a lysine to a stop codon within coding exon 2. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Although biallelic loss of function alterations in JUP have been associated with autosomal recessive Naxos disease, haploinsufficiency for JUP has not been clearly established as a mechanism of disease for autosomal dominant JUP-related arrhythmogenic right ventricular cardiomyopathy (ARVC). Based on the supporting evidence, this variant is expected to be causative of autosomal recessive Naxos disease when present along with a second pathogenic variant on the other allele; however, its clinical significance for autosomal dominant JUP-related ARVC is unclear. |
| Labcorp Genetics |
RCV005216076 | SCV005853189 | pathogenic | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2024-11-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys124*) in the JUP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in JUP are known to be pathogenic (PMID: 10902626). This variant is not present in population databases (gnomAD no frequency). 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: 2625419). For these reasons, this variant has been classified as Pathogenic. |