Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001938620 | SCV002195698 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2022-02-09 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt JAG1 protein function. This variant has not been reported in the literature in individuals affected with JAG1-related conditions. This variant is present in population databases (rs774372899, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 805 of the JAG1 protein (p.Arg805Gln). |
| Ambry Genetics | RCV002449592 | SCV002733768 | uncertain significance | Cardiovascular phenotype | 2021-11-24 | criteria provided, single submitter | clinical testing | The p.R805Q variant (also known as c.2414G>A), located in coding exon 20 of the JAG1 gene, results from a G to A substitution at nucleotide position 2414. The arginine at codon 805 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |