ClinVar Miner

Submissions for variant NM_002755.3(MAP2K1):c.608A>G (rs727503996)

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Total submissions: 3
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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, http://gnomad.broadinstitute.org). 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics 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

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