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NM_030662.4(MAP2K2):c.401A>G (p.Tyr134Cys) AND RASopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 30, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000154507.14

Allele description [Variation Report for NM_030662.4(MAP2K2):c.401A>G (p.Tyr134Cys)]

NM_030662.4(MAP2K2):c.401A>G (p.Tyr134Cys)

Gene:
MAP2K2:mitogen-activated protein kinase kinase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.3
Genomic location:
Preferred name:
NM_030662.4(MAP2K2):c.401A>G (p.Tyr134Cys)
Other names:
NM_030662.3(MAP2K2):c.401A>G
HGVS:
  • NC_000019.10:g.4110558T>C
  • NG_007996.1:g.18571A>G
  • NM_030662.4:c.401A>GMANE SELECT
  • NP_109587.1:p.Tyr134Cys
  • NP_109587.1:p.Tyr134Cys
  • LRG_750t1:c.401A>G
  • LRG_750:g.18571A>G
  • LRG_750p1:p.Tyr134Cys
  • NC_000019.9:g.4110556T>C
  • NM_030662.3:c.401A>G
Protein change:
Y134C
Links:
dbSNP: rs727504370
NCBI 1000 Genomes Browser:
rs727504370
Molecular consequence:
  • NM_030662.4:c.401A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
RASopathy
Synonyms:
rasopathies; Noonan spectrum disorder
Identifiers:
MONDO: MONDO:0021060; MedGen: C5555857

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000551456Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 30, 2022) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options.

Senawong T, Phuchareon J, Ohara O, McCormick F, Rauen KA, Tetsu O.

Hum Mol Genet. 2008 Feb 1;17(3):419-30. Epub 2007 Nov 2.

PubMed [citation]
PMID:
17981815

Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors.

Anastasaki C, Estep AL, Marais R, Rauen KA, Patton EE.

Hum Mol Genet. 2009 Jul 15;18(14):2543-54. doi: 10.1093/hmg/ddp186. Epub 2009 Apr 17.

PubMed [citation]
PMID:
19376813
PMCID:
PMC2701326
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000551456.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MAP2K2 function (PMID: 17981815, 18413255, 19376813). 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 MAP2K2 protein function. ClinVar contains an entry for this variant (Variation ID: 177868). This variant is also known as MEK2 Y134C. This missense change has been observed in individuals with cardio-facio-cutaneous syndrome (PMID: 18039235, 18413255, 23885229). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 134 of the MAP2K2 protein (p.Tyr134Cys).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 16, 2024