ClinVar Miner

Submissions for variant NM_014009.4(FOXP3):c.542G>T (p.Ser181Ile)

dbSNP: rs1602686006
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000805851 SCV000945824 uncertain significance Insulin-dependent diabetes mellitus secretory diarrhea syndrome 2018-08-12 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with FOXP3-related disease. 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with isoleucine at codon 181 of the FOXP3 protein (p.Ser181Ile). The serine residue is weakly conserved and there is a large physicochemical difference between serine and isoleucine. This variant also falls at the last nucleotide of exon 5 of the FOXP3 coding sequence, which is part of the consensus splice site for this exon.

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.