ClinVar Miner

Submissions for variant NM_002755.4(MAP2K1):c.355C>T (p.His119Tyr)

dbSNP: rs730880503
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000505738 SCV000207942 pathogenic not provided 2019-09-17 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26633542, 24755471, 26582713)
Labcorp Genetics (formerly Invitae), Labcorp RCV001385117 SCV001584864 pathogenic RASopathy 2021-09-17 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: 12370306). 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 40741). This missense change has been observed in individual(s) with clinical features of MAP2K1-related disorders (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 119 of the MAP2K1 protein (p.His119Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine.
Undiagnosed Diseases Network, NIH RCV001526460 SCV001736877 uncertain significance MAP2K1-related rasopathy-like syndrome 2021-04-28 criteria provided, single submitter clinical testing
GenomeConnect - CFC International RCV001089756 SCV001245249 not provided MAP2K1-related disorder no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 08-30-2011 by Lab or GTR ID 26957. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant.

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