Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000731732 | SCV000859581 | uncertain significance | not provided | 2018-02-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001855764 | SCV002136343 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2023-08-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1096 of the JAG1 protein (p.Arg1096Trp). This variant is present in population databases (rs537986153, gnomAD 0.03%). This missense change has been observed in individual(s) with JAG1-related conditions (PMID: 31475041, 34399559). ClinVar contains an entry for this variant (Variation ID: 596031). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
Ambry Genetics | RCV003165975 | SCV003855103 | uncertain significance | Cardiovascular phenotype | 2023-03-13 | criteria provided, single submitter | clinical testing | The p.R1096W variant (also known as c.3286C>T), located in coding exon 26 of the JAG1 gene, results from a C to T substitution at nucleotide position 3286. The arginine at codon 1096 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration was reported in a prenatal cohort in a fetus with increased nuchal translucency and absent nasal bone (Choy KW et al. Front Genet, 2019 Aug;10:761). This alteration was also reported in a thoracic aortic aneurysm and dissection (TAAD) cohort (Li Y et al. Am J Transl Res, 2021 May;13:4281-4295). 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 alteration remains unclear. |