Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001215387 | SCV001387127 | uncertain significance | Alagille syndrome due to a JAG1 point mutation | 2019-04-02 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual with clinical features of Allagile syndrome (Invitae). This sequence change replaces isoleucine with asparagine at codon 39 of the JAG1 protein (p.Ile39Asn). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and asparagine. |