ClinVar Miner

Submissions for variant NM_004612.4(TGFBR1):c.648T>G (p.Phe216Leu) (rs863223809)

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
GeneDx RCV000196750 SCV000250876 uncertain significance not provided 2014-05-29 criteria provided, single submitter clinical testing p.Phe216Leu (TTT>TTG): c.648 T>G in exon 4 of the TGFBR1 gene (NM_004612.2) The F216L variant of unknown significance identified in the TGFBR1 gene has not been published as a mutation or reported as a benign polymorphism to our knowledge. The F216L variant 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. This substitution occurs at a position that is fully conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The F216L variant is located within the serine-threonine kinase domain where other missense mutations have been reported in association with Loeys-Dietz syndrome/ TAAD (Stheneur et al., 2008), supporting the functional importance of this region of the protein. However, the F216L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD

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.