Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000696810 | SCV000825389 | pathogenic | Alagille syndrome due to a JAG1 point mutation | 2021-04-02 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tyrosine at codon 293 of the JAG1 protein (p.Cys293Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. For these reasons, this variant has been classified as Pathogenic. 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 been observed in individual(s) with Alagille syndrome (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 574788). This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002369896 | SCV002685148 | uncertain significance | Cardiovascular phenotype | 2014-08-11 | criteria provided, single submitter | clinical testing | The p.C293Y variant (also known as c.878G>A), located in coding exon 6 of the JAG1 gene, results from a G to A substitution at nucleotide position 878. The cysteine at codon 293 is replaced by tyrosine, an amino acid with highly dissimilar 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, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |