ClinVar Miner

Submissions for variant NM_000192.3(TBX5):c.755G>C (p.Ser252Thr) (rs863223776)

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
Centre de Biologie Pathologie Génétique,Centre Hospitalier Universitaire de Lille RCV000782337 SCV000920858 likely pathogenic Holt-Oram syndrome 2018-06-14 no assertion criteria provided clinical testing
GeneDx RCV000255260 SCV000321955 likely pathogenic not provided 2015-12-08 criteria provided, single submitter clinical testing The S252T missense variant has not been previously reported as disease causing nor as a benign polymorphism. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. S252T alters the last base of exon 7, immediately 5' of the canonical GT" splice donor site. In silico analysis with several different splice algorithms predicts that this splice donor site is abolished or altered, potentially leading to aberrant gene splicing. In addition, two other nucleotide changes (G>T aka S252I and G>A aka S252N) at this highly conserved position have been seen in multiple patients referred for clinical testing for HOS at GeneDx. Although the effect of these variants on gene splicing has not yet been demonstrated, S252I has been reported in the literature in association with Holt-Oram syndrome (Cross et al., 2000). In summary, we consider S252T to be likely pathogenic; however, the possibility that it is benign cannot be excluded."

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.