ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1129C>T (p.Arg377Cys)

dbSNP: rs368564000
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001226347 SCV001398659 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 377 of the JUP protein (p.Arg377Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. 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. 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: "Probably Damaging"; 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 RCV002320210 SCV002608412 uncertain significance Cardiovascular phenotype 2019-06-06 criteria provided, single submitter clinical testing The p.R377C variant (also known as c.1129C>T), located in coding exon 6 of the JUP gene, results from a C to T substitution at nucleotide position 1129. The arginine at codon 377 is replaced by cysteine, an amino acid with highly dissimilar properties. Other alterations affecting the same amino acid, p.R377H (c.1130G>A) and p.R377S (c.1129C>A), have been reported in association with cardiomyopathy (Zhou X et al. Eur J Med Genet, 2015 Apr;58:258-65; Walsh R et al. Genet. Med., 2017 02;19:192-203). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.