ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.521C>T (p.Ala174Val)

gnomAD frequency: 0.00002  dbSNP: rs146786437
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000247465 SCV000320261 uncertain significance Cardiovascular phenotype 2016-07-25 criteria provided, single submitter clinical testing The p.A174V variant (also known as c.521C>T), located in coding exon 3 of the JUP gene, results from a C to T substitution at nucleotide position 521. The alanine at codon 174 is replaced by valine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs146786437. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.01% (1/13006) total alleles studied and 0.01% (1/8600) European American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae RCV001205869 SCV001377149 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2022-05-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 174 of the JUP protein (p.Ala174Val). This variant is present in population databases (rs146786437, gnomAD 0.009%). This missense change has been observed in individual(s) with JUP-related conditions (PMID: 32880476). ClinVar contains an entry for this variant (Variation ID: 264367). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Fulgent Genetics, Fulgent Genetics RCV001205869 SCV002816774 uncertain significance Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2021-09-16 criteria provided, single submitter clinical testing

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.