ClinVar Miner

Submissions for variant NM_199292.3(TH):c.1394C>G (p.Ser465Cys) (rs767211543)

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
Counsyl RCV000670046 SCV000794857 uncertain significance Segawa syndrome, autosomal recessive 2017-10-18 criteria provided, single submitter clinical testing
Invitae RCV000822614 SCV000963424 uncertain significance Dystonia 2018-07-10 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 465 of the TH protein (p.Ser465Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs767211543, ExAC 0.002%). This variant has been observed in an individual affected with TH-deficiency; however, a second TH variant was not detected in that individual (PMID: 28186668). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.