Submissions for variant NM_002230.4(JUP):c.401A>G (p.Gln134Arg)

dbSNP: rs1057518313

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000412952	SCV000491846	uncertain significance	not specified	2016-11-18	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the JUP gene. The Q134R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q134R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Ambry Genetics	RCV002356510	SCV002619642	uncertain significance	Cardiovascular phenotype	2019-02-12	criteria provided, single submitter	clinical testing	The p.Q134R variant (also known as c.401A>G), located in coding exon 2 of the JUP gene, results from an A to G substitution at nucleotide position 401. The glutamine at codon 134 is replaced by arginine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005222917	SCV005864926	uncertain significance	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2024-11-10	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 134 of the JUP protein (p.Gln134Arg). 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: 373265). 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.