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NM_002755.4(MAP2K1):c.199G>A (p.Asp67Asn) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 31, 2014
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:
RCV000844673.12

Allele description [Variation Report for NM_002755.4(MAP2K1):c.199G>A (p.Asp67Asn)]

NM_002755.4(MAP2K1):c.199G>A (p.Asp67Asn)

Gene:
MAP2K1:mitogen-activated protein kinase kinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q22.31
Genomic location:
Preferred name:
NM_002755.4(MAP2K1):c.199G>A (p.Asp67Asn)
Other names:
p.D67N:GAC>AAC; NM_002755.3(MAP2K1):c.199G>A
HGVS:
  • NC_000015.10:g.66435145G>A
  • NG_008305.1:g.53273G>A
  • NM_002755.4:c.199G>AMANE SELECT
  • NP_002746.1:p.Asp67Asn
  • NP_002746.1:p.Asp67Asn
  • LRG_725t1:c.199G>A
  • LRG_725:g.53273G>A
  • LRG_725p1:p.Asp67Asn
  • NC_000015.9:g.66727483G>A
  • NM_002755.3:c.199G>A
Protein change:
D67N
Links:
dbSNP: rs727504317
NCBI 1000 Genomes Browser:
rs727504317
Molecular consequence:
  • NM_002755.4:c.199G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
6

Condition(s)

Name:
Noonan syndrome (NS)
Synonyms:
Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:
MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950
Name:
Cardio-facio-cutaneous syndrome
Synonyms:
Cardiofaciocutaneous syndrome; CFC syndrome
Identifiers:
MONDO: MONDO:0015280; MedGen: C1275081; Orphanet: 1340; OMIM: PS115150

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000204064Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Oct 31, 2014) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided66not providednot providednot providedclinical testing

Citations

PubMed

Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome.

Nava C, Hanna N, Michot C, Pereira S, Pouvreau N, Niihori T, Aoki Y, Matsubara Y, Arveiler B, Lacombe D, Pasmant E, Parfait B, Baumann C, Héron D, Sigaudy S, Toutain A, Rio M, Goldenberg A, Leheup B, Verloes A, Cavé H.

J Med Genet. 2007 Dec;44(12):763-71. Epub 2007 Aug 17.

PubMed [citation]
PMID:
17704260
PMCID:
PMC2652823

Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy.

Estep AL, Palmer C, McCormick F, Rauen KA.

PLoS One. 2007 Dec 5;2(12):e1279.

PubMed [citation]
PMID:
18060073
PMCID:
PMC2093994
See all PubMed Citations (5)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204064.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedclinical testing PubMed (5)

Description

The p.Asp67Asn variant in MAP2K1 has been identified in 9 individuals with clini cal features of Noonan syndrome and/or Cardio-facio-cutaneous syndrome including 2 de novo occurences (Nava 2007, LMM unpublished data). This variant was absent from large population studies. In vitro functional studies provide some evidenc e that the p.Asp67Asn variant may impact protein function (Estep 2007). However, these types of assays may not accurately represent biological function. This va riant has also been reported in tumor samples from 2 individuals with colon canc er (Murugan 2009, Choi 2012). In summary, this variant meets our criteria to be classified as pathogenic for RASopathies in an autosomal dominant manner (http:/ /www.partners.org/personalizedmedicince/LMM) based upon de novo occurrences, abs ence from controls, and functional evidence.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided6not provided6not provided

Last Updated: Oct 26, 2024