Total submissions: 3
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, |
RCV001205869 | SCV002816774 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2021-09-16 | criteria provided, single submitter | clinical testing |