ClinVar Miner

Submissions for variant NM_002755.4(MAP2K1):c.383G>T (p.Gly128Val)

dbSNP: rs121908596
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000211725 SCV000061254 likely pathogenic Cardio-facio-cutaneous syndrome 2014-11-21 criteria provided, single submitter clinical testing The p.Gly128Val variant in MAP2K1 has been previously identified in 2 individual s with clinical features of Cardio-facio-cutaneous syndrome (Schulz 2008, LMM un published data) and was identified to occur de novo in one of these individuals (Schulz 2008). It was absent from large population studies. Computational predic tion tools and conservation analysis suggest that the p.Gly128Val variant may im pact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the p.Gly128Val variant is likely pathogenic, though additional studies are required to fully establish its clinical significance.
Molecular Diagnostics Lab, Nemours Children's Health, Delaware RCV000207493 SCV000263047 likely pathogenic not provided 2015-07-21 criteria provided, single submitter clinical testing
GeneDx RCV000207493 SCV000808249 pathogenic not provided 2023-06-12 criteria provided, single submitter clinical testing Transgenic Zebra fish model with the p.(G128V) variant demonstrated features consistent with a RASopathy (Jindal et al., 2017); Identified in a newborn patient with congenital heart disease in published literature (Hakami et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 24803665, 26918529, 25370473, 22753777, 19156172, 26399658, 22177953, 29493581, 18042262, 31972311, 28049852)
Labcorp Genetics (formerly Invitae), Labcorp RCV001234104 SCV001406731 pathogenic RASopathy 2021-10-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MAP2K1 function (PMID: 19376813, 28049852). 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 expected to disrupt MAP2K1 protein function. ClinVar contains an entry for this variant (Variation ID: 13352). This missense change has been observed in individual(s) with cardio-facio-cutaneous syndrome (PMID: 1804226, 18039235, 18413255, 21062266). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 128 of the MAP2K1 protein (p.Gly128Val).
OMIM RCV000043673 SCV000034529 pathogenic Cardiofaciocutaneous syndrome 3 2008-01-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.