Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000619191 | SCV000736397 | uncertain significance | Cardiovascular phenotype | 2018-03-07 | criteria provided, single submitter | clinical testing | The p.G309R variant (also known as c.925G>C), located in coding exon 7 of the JAG1 gene, results from a G to C substitution at nucleotide position 925. The glycine at codon 309 is replaced by arginine, an amino acid with dissimilar properties. In one study, this alteration was detected in an individual with tetralogy of Fallot and some dysmorphic features (Guida V et al. Clin Genet. 2011;80:591-4). This amino acid position is not well conserved in available vertebrate species, and arginine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001042284 | SCV001205959 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2023-09-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 518844). This missense change has been observed in individual(s) with isolated Tetralogy of Fallot (PMID: 22040217). This variant is present in population databases (rs750195672, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 309 of the JAG1 protein (p.Gly309Arg). 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. 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. |
Prevention |
RCV003424189 | SCV004118543 | uncertain significance | JAG1-related condition | 2023-04-04 | criteria provided, single submitter | clinical testing | The JAG1 c.925G>C variant is predicted to result in the amino acid substitution p.Gly309Arg. This variant was reported in an individual with tetralogy of Fallot (Guida et al. 2011. PubMed ID: 22040217). This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-10632860-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |