ClinVar Miner

Submissions for variant NM_012452.2(TNFRSF13B):c.58C>T (p.Arg20Cys)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735375 SCV000854529 uncertain significance Seizures; Micrognathia; Cognitive impairment; Cafe-au-lait spot; Frontal bossing; High forehead; Abnormality of the basal ganglia; Thoracic scoliosis; Abnormal basal ganglia MRI signal intensity criteria provided, single submitter clinical testing
Invitae RCV000700484 SCV000829241 uncertain significance Common variable immunodeficiency 2 2018-12-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 20 of the TNFRSF13B protein (p.Arg20Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs200013015, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual affected with hyper-IgM syndrome or common variable immunodeficiency (PMID: 20652909). This variant has also been reported in an individual affected with systemic lupus erythematosus (SLE) (PMID: 17464555). However, this variant was absent in this individual's son, who was also affected with SLE, which suggests that this variant was not likely a primary cause of disease in this family. 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 tolerated. Experimental studies performed on cells derived from the proband carrying the p.Arg20Cys variant demonstrated modestly reduced TACI expression and APRIL binding, however, similar results were seen in cells derived from this individual's affected son, who did not carry this variant (PMID: 17464555). This suggests that the presence of the p.Arg20Cys variant is unlikely to be the cause of the experimental findings seen in these individuals and the clinical significance of this variant remains 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.