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

gnomAD frequency: 0.00001  dbSNP: rs794729054

Total submissions: 6

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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001852359	SCV002196376	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2024-12-22	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 283 of the JUP protein (p.Lys283Asn). This variant is present in population databases (rs794729054, gnomAD 0.003%). 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). 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 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	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