ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.791C>A (p.Thr264Lys) (rs1595001710)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Human Genetics, University Hospital Magdeburg RCV001250766 SCV001426177 pathogenic Noonan syndrome 9 2020-07-02 criteria provided, single submitter clinical testing This variant has been previously reported as pathogenic (PS1). It is absent from gnomAD (PM2). The variant is assumed to be de novo, but without confirmation of paternity and maternity (PM6). The REVEL Score of this variant is 0.713 (PP3) and the variant has been cllassified as likely pathogenic in ClinVar (PP5).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001269182 SCV001448466 likely pathogenic Rasopathy 2020-11-23 criteria provided, single submitter clinical testing Variant summary: SOS2 c.791C>A (p.Thr264Lys) results in a non-conservative amino acid change located in the Ras guanine-nucleotide exchange factors catalytic domain (IPR001895) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251280 control chromosomes (gnomAD). c.791C>A has been reported in the literature in individuals affected with Noonan Syndrome (Cordeddu_2015, Lissewski_2020). These data indicate that the variant may be associated with disease. Variant was functionally assessed in vitro using HEK293 cells and resulted in higher levels of GTP-bound RAS and increased signaling of Ras/MAPK pathway consistent with the known molecular mechanism of disease (Cordeddu_2015, Tidyman_2016). Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Yale Center for Mendelian Genomics,Yale University RCV000845124 SCV000987060 likely pathogenic Noonan syndrome 2015-08-03 no assertion criteria provided literature only
Service de Génétique Moléculaire,Hôpital Robert Debré RCV000845124 SCV001426698 pathogenic Noonan syndrome no assertion criteria provided clinical testing

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.