ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.849G>T (p.Lys283Asn)

gnomAD frequency: 0.00001  dbSNP: rs794729054
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183510 SCV000235970 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing The K283N variant of uncertain significance in the JUP gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 3/111,686 (0.003%) European (non-Finnish) alleles in large population cohorts (Lek et al., 2016). The K283N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV001852359 SCV002196376 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 283 of the JUP protein (p.Lys283Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC 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: 201832). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 RCV002444742 SCV002678518 uncertain significance Cardiovascular phenotype 2023-10-23 criteria provided, single submitter clinical testing The p.K283N variant (also known as c.849G>T), located in coding exon 4 of the JUP gene, results from a G to T substitution at nucleotide position 849. The lysine at codon 283 is replaced by asparagine, an amino acid with 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.
Fulgent Genetics, Fulgent Genetics RCV001852359 SCV002779567 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-04-04 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000183510 SCV001739534 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000183510 SCV001969864 uncertain significance not provided no assertion criteria provided clinical testing

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