ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1399T>G (p.Ser467Ala) (rs869025606)

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
GeneDx RCV000346147 SCV000329762 pathogenic not provided 2016-04-07 criteria provided, single submitter clinical testing The S467A variant in the BRAF gene has been published previously in association with cardio-facio-cutaneous syndrome (Rodriguez-Viciana et al., 2006). The 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. BRAF has a low rate of benign missense variation and missense variants are a common mechanism of disease in this gene. S467A is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the ATP-binding domain that is conserved across species. In addition, in vitro studies have shown that S467A results in higher levels of MEK and ERK phosphorylation. Missense variants in nearby residues (G464R/V, F468S, G469R/E, T470P) have been reported in the Human Gene Mutation Database in association with cardio-facio-cutaneous syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret S467A to be a pathogenic variant.
GeneReviews RCV000208777 SCV000264631 pathogenic Cardio-facio-cutaneous syndrome 2016-03-03 no assertion criteria provided literature only

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.