Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000619870 | SCV000737502 | uncertain significance | Cardiovascular phenotype | 2016-05-17 | criteria provided, single submitter | clinical testing | The p.V274M variant (also known as c.820G>A), located in coding exon 4 of the JUP gene, results from a G to A substitution at nucleotide position 820. The valine at codon 274 is replaced by methionine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. 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 | RCV001326335 | SCV001517362 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2020-02-21 | criteria provided, single submitter | clinical testing | 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with JUP-related conditions. ClinVar contains an entry for this variant (Variation ID: 519238). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 274 of the JUP protein (p.Val274Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. |
| Fulgent Genetics, |
RCV001326335 | SCV002814344 | uncertain significance | Naxos disease; Arrhythmogenic right ventricular dysplasia 12 | 2021-07-19 | criteria provided, single submitter | clinical testing |