ClinVar Miner

Submissions for variant NM_002755.4(MAP2K1):c.69C>T (p.Thr23=) (rs140749690)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000523509 SCV000616549 likely benign Rasopathy 2017-05-09 reviewed by expert panel curation The filtering allele frequency of the c.69C>T (p.Thr23=) variant in the MAP2K1 gene is 0.0484% (4/2820) of African 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)
GeneDx RCV000154751 SCV000170175 benign not specified 2013-12-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154751 SCV000204431 likely benign not specified 2016-02-04 criteria provided, single submitter clinical testing p.Thr23Thr in exon 1 of MAP2K1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.1% (4/2820) of A frican chromosomes by the Exome Aggregation Consortium Project (ExAC, http://exa c.broadinstitute.org/; dbSNP rs140749690).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154751 SCV000917606 benign not specified 2017-10-04 criteria provided, single submitter clinical testing Variant summary: The MAP2K1 c.69C>T (p.Thr23Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. MutationTaster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may introduce an SF2/ASF ESE site at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in 25/188032 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.001386 (24/17310). This frequency is about 554 times the estimated maximal expected allele frequency of a pathogenic MAP2K1 variant (0.0000025), strongly suggesting this is likely a benign polymorphism found primarily in populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign or benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Invitae RCV000523509 SCV001008992 benign Rasopathy 2020-10-13 criteria provided, single submitter clinical testing

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