Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001901873 | SCV002128237 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2021-06-20 | 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 not expected to disrupt JAG1 protein function. This variant has not been reported in the literature in individuals with JAG1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 937 of the JAG1 protein (p.Arg937Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. |
| Ambry Genetics | RCV002440935 | SCV002748116 | uncertain significance | Cardiovascular phenotype | 2021-08-10 | criteria provided, single submitter | clinical testing | The p.R937W variant (also known as c.2809C>T), located in coding exon 23 of the JAG1 gene, results from a C to T substitution at nucleotide position 2809. The arginine at codon 937 is replaced by tryptophan, an amino acid with dissimilar 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. |