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NM_002834.5(PTPN11):c.227A>G (p.Glu76Gly) AND Juvenile myelomonocytic leukemia

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Oct 18, 2015
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:
RCV000014266.11

Allele description [Variation Report for NM_002834.5(PTPN11):c.227A>G (p.Glu76Gly)]

NM_002834.5(PTPN11):c.227A>G (p.Glu76Gly)

Gene:
PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.13
Genomic location:
Preferred name:
NM_002834.5(PTPN11):c.227A>G (p.Glu76Gly)
Other names:
p.E76G:GAG>GGG
HGVS:
  • NC_000012.12:g.112450407A>G
  • NG_007459.1:g.36676A>G
  • NM_001330437.2:c.227A>G
  • NM_001374625.1:c.224A>G
  • NM_002834.4:c.227A>G
  • NM_002834.5:c.227A>GMANE SELECT
  • NM_080601.3:c.227A>G
  • NP_001317366.1:p.Glu76Gly
  • NP_001361554.1:p.Glu75Gly
  • NP_002825.3:p.Glu76Gly
  • NP_542168.1:p.Glu76Gly
  • LRG_614t1:c.227A>G
  • LRG_614:g.36676A>G
  • NC_000012.11:g.112888211A>G
  • NM_002834.3:c.227A>G
  • Q06124:p.Glu76Gly
Protein change:
E75G; GLU76GLY
Links:
UniProtKB: Q06124#VAR_015999; OMIM: 176876.0016; dbSNP: rs121918465
NCBI 1000 Genomes Browser:
rs121918465
Molecular consequence:
  • NM_001330437.2:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.224A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.227A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Juvenile myelomonocytic leukemia (JMML)
Synonyms:
LEUKEMIA, JUVENILE MYELOMONOCYTIC, SOMATIC
Identifiers:
MONDO: MONDO:0011908; MedGen: C0349639; Orphanet: 86834; OMIM: 607785; Human Phenotype Ontology: HP:0012209

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  • Hypergammaglobulinemia
    Hypergammaglobulinemia
    An excess of GAMMA-GLOBULINS in the serum due to chronic infections or PARAPROTEINEMIAS.<br/>Year introduced: 1972(1969)
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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000034515OMIM
no assertion criteria provided
Pathogenic
(Jun 1, 2003) 		somaticliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000204032Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Oct 18, 2015) 		somaticclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticnot provided22not providednot providednot providedclinical testing, literature only

Citations

PubMed

Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia.

Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, Hählen K, Hasle H, Licht JD, Gelb BD.

Nat Genet. 2003 Jun;34(2):148-50.

PubMed [citation]
PMID:
12717436

The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease.

Kratz CP, Niemeyer CM, Castleberry RP, Cetin M, Bergsträsser E, Emanuel PD, Hasle H, Kardos G, Klein C, Kojima S, Stary J, Trebo M, Zecca M, Gelb BD, Tartaglia M, Loh ML.

Blood. 2005 Sep 15;106(6):2183-5. Epub 2005 May 31.

PubMed [citation]
PMID:
15928039
PMCID:
PMC1895140
See all PubMed Citations (12)

Details of each submission

From OMIM, SCV000034515.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

See 176876.0014 and Tartaglia et al. (2003).

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

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204032.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (12)

Description

The p.Glu76Gly variant in PTPN11 has been reported as a somatic change in >10 in dividuals with juvenile myelomonocytic leukemia (JMML), acute myeloid leukemia ( AML), or childhood acute lymphoblastic leukemia (ALL; Tartaglia 2003, Tartaglia 2004, Loh 2004, Kratz 2005). In addition, many other variants at this position h ave been frequently identified as a somatic change in individuals with JMML, AML , and ALL, and codon 76 in PTPN11 has been described as the mutational hot-spot for JMML (Tartaglia 2003). It was absent from large population studies. In summa ry, this variant meets our criteria to be classified as pathogenic for JMML.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1somaticnot providednot providednot providednot provided2not provided2not provided

Last Updated: Sep 29, 2024