ClinVar Miner

Submissions for variant NM_030662.3(MAP2K2):c.890G>A (p.Arg297Gln) (rs140111079)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000680326 SCV000338001 uncertain significance not provided 2015-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000680326 SCV000617078 uncertain significance not provided 2017-07-11 criteria provided, single submitter clinical testing The R297Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is observed in 3/39968 (0.0075%) alleles from individuals of European background in the ExAC dataset (Lek et al., 2016). R297Q 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. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000690698 SCV000818398 uncertain significance Rasopathy 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 297 of the MAP2K2 protein (p.Arg297Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs140111079, ExAC 0.008%). This variant has not been reported in the literature in individuals with MAP2K2-related disease. ClinVar contains an entry for this variant (Variation ID: 285121). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Fulgent Genetics,Fulgent Genetics RCV000764204 SCV000895207 uncertain significance Cardiofaciocutaneous syndrome 4 2018-10-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000764204 SCV001159965 uncertain significance Cardiofaciocutaneous syndrome 4 2018-09-28 criteria provided, single submitter clinical testing The MAP2K2 c.890G>A; p.Arg297Gln variant (rs140111079), to our knowledge, is not described in the medical literature but is reported as a variant of uncertain significance in ClinVar (Variation ID: 285121). It is observed in the Non-Finnish European population at an overall frequency of 0.006% (7/114722 alleles) in the Genome Aggregation Database. The arginine at codon 297 is highly conserved, but computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. Due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty.

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