ClinVar Miner

Submissions for variant NM_030662.4(MAP2K2):c.826G>C (p.Glu276Gln)

gnomAD frequency: 0.00001  dbSNP: rs889422963
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412732 SCV000491471 uncertain significance not specified 2016-03-22 criteria provided, single submitter clinical testing The E276Q variant in the MAP2K2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E276Q 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. The E276Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense variant in nearby residue K273R has been reported in the Human Gene Mutation Database in association with cardio-facio-cutaneous syndrome (Stenson et al., 2014). Therefore, given the available data, interpret E276Q as a variant of uncertain significance
Labcorp Genetics (formerly Invitae), Labcorp RCV001861423 SCV002247120 uncertain significance RASopathy 2023-06-16 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt MAP2K2 function. ClinVar contains an entry for this variant (Variation ID: 372931). This variant has not been reported in the literature in individuals affected with MAP2K2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 276 of the MAP2K2 protein (p.Glu276Gln).

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