ClinVar Miner

Submissions for variant NM_002755.4(MAP2K1):c.608A>G (p.Glu203Gly) (rs727503996)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV001250390 SCV001424752 pathogenic Rasopathy 2020-05-18 reviewed by expert panel curation The c.608A>G (p.Glu203Gly) variant in MAP2K1 was absent from large population studies (PM2; gnomAD, It has been reported in 3 probands with clinical features of a RASopathy (PS4_Moderate; SCV000965973.1,SCV000202961.7, GeneDx internal data). The variant arose de novo in two of the probands without confirmed parentage (PM6_Strong; SCV000965973.1, SCV000202961.7). Computational prediction tools and conservation analysis suggest that the c.608A>G (p.Glu203Gly) variant may impact protein function (PP3). Finally, the variant is located in MAP2K1, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID: 29493581). In summary, this variant meets criteria to be classified as pathogenic for RASopathies in an autosomal dominant manner. Rasopathy-specific ACMG/AMP criteria applied (PMID:29493581): PM6_Strong, PS4_Moderate, PM2, PP3, PP2.
Eurofins NTD, LLC RCV000153454 SCV000202961 uncertain significance not provided 2013-11-27 criteria provided, single submitter clinical testing
Service de Génétique Moléculaire,Hôpital Robert Debré RCV000824938 SCV000965973 likely 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.