ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.383C>A (p.Pro128Gln)

dbSNP: rs267607230
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV004760323 SCV000616540 pathogenic RASopathy 2024-09-17 reviewed by expert panel curation The c.383C>A variant in the MAP2K2 gene is a missense variant predicted to cause substitution of proline by glutamine at amino acid 128 (p.Pro128Gln). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational predictor REVEL gives a score of 0.928 (PP3). This variant is located in a functional domain supporting pathogenicity (PM1). This variant has been reported to segregate with clinical features of a RASopathy in at least 7 family members of the proband (PS4_Supporting, PP1_Strong; 20358587). ERK phosphorylation assay showed that this variant led to increased ERK phosphorylation compared to wild-type (PS3_P; PMID 20358587). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: PP1_Strong, PM1, PS3_Supporting, PS4_Supporting, PM2_Supporting, PP3 (Specification Version 2.1, 09/17/2024)
GeneDx RCV000158021 SCV000207956 pathogenic not provided 2013-05-27 criteria provided, single submitter clinical testing p.Pro128Gln (CCG>CAG): c.383 C>A in exon 3 of the MAP2K2 gene (NM_030662.3). The P128Q missense mutation in the MAP2K2 gene has been reported previously in association with cardio-facio-cutaneous (CFC) syndrome (Rauen et al., 2009). Additionally, another mutation at the same codon (P128R) has been reported in association with CFC syndrome (Narumi et al., 2007). The variant is found in NOONAN panel(s).
OMIM RCV000008764 SCV000028973 pathogenic Cardiofaciocutaneous syndrome 4 2010-04-01 no assertion criteria provided literature only
GeneReviews RCV000208770 SCV000264642 not provided Cardio-facio-cutaneous syndrome no assertion provided literature only

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