Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001877653 | SCV002139074 | uncertain significance | Hypertrophic cardiomyopathy | 2021-02-19 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 284 of the JPH2 protein (p.Asp284Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with JPH2-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: "Tolerated"; 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 | RCV003355599 | SCV004053108 | uncertain significance | Cardiovascular phenotype | 2023-07-05 | criteria provided, single submitter | clinical testing | The p.D284E variant (also known as c.852C>A), located in coding exon 2 of the JPH2 gene, results from a C to A substitution at nucleotide position 852. The aspartic acid at codon 284 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |