ClinVar Miner

Submissions for variant NM_000206.2(IL2RG):c.675C>G (p.Ser225Arg) (rs1569479913)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000686497 SCV000814018 uncertain significance X-linked severe combined immunodeficiency 2018-08-02 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 225 of the IL2RG protein (p.Ser225Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with IL2RG-related disease. A different variant (c.675C>A) giving rise to the same protein effect observed here (p.Ser225Arg) has been reported in an individual affected with T-B+NK- X-linked severe combined immunodeficiency (PMID: 26547715), indicating that this residue may be critical for protein function. 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. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.