ClinVar Miner

Submissions for variant NM_030662.3(MAP2K2):c.847G>T (p.Val283Leu) (rs185999703)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000520355 SCV000616567 likely benign Rasopathy 2017-05-09 reviewed by expert panel curation The filtering allele frequency of the c.847G>T (p.Val283Leu) variant in the MAP2K2 gene is 0.0448% (6/5824) of East Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)
Invitae RCV000520355 SCV001531579 uncertain significance Rasopathy 2020-09-24 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 283 of the MAP2K2 protein (p.Val283Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs185999703, ExAC 0.1%). This variant has not been reported in the literature in individuals with MAP2K2-related conditions. ClinVar contains an entry for this variant (Variation ID: 448950). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MAP2K2 protein function. 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.

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