Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004635692 | SCV005127510 | uncertain significance | Cardiovascular phenotype | 2024-04-26 | criteria provided, single submitter | clinical testing | The p.D149A variant (also known as c.446A>C), located in coding exon 4 of the JAG1 gene, results from an A to C substitution at nucleotide position 446. The aspartic acid at codon 149 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV005102239 | SCV005823857 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2024-04-04 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 149 of the JAG1 protein (p.Asp149Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with JAG1-related conditions. 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 with a negative predictive value of 95%. 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. |