NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp) AND Noonan Syndrome with Juvenile Myelomonocytic Leukemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 23, 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:: RCV000824739.12

Allele description [Variation Report for NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)]

NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)

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.184T>G (p.Tyr62Asp)

Other names:

p.Y62D:TAC>GAC

HGVS:

NC_000012.12:g.112450364T>G
NG_007459.1:g.36633T>G
NM_001330437.2:c.184T>G
NM_001374625.1:c.181T>G
NM_002834.5:c.184T>GMANE SELECT
NM_080601.3:c.184T>G
NP_001317366.1:p.Tyr62Asp
NP_001317366.1:p.Tyr62Asp
NP_001361554.1:p.Tyr61Asp
NP_002825.3:p.Tyr62Asp
NP_002825.3:p.Tyr62Asp
NP_542168.1:p.Tyr62Asp
LRG_614t1:c.184T>G
LRG_614:g.36633T>G
LRG_614p1:p.Tyr62Asp
NC_000012.11:g.112888168T>G
NM_001330437.1:c.184T>G
NM_002834.3:c.184T>G
NM_002834.4(PTPN11):c.184T>G
NM_002834.4:c.184T>G
Q06124:p.Tyr62Asp

Protein change:

Y61D; TYR62ASP

Links:

UniProtKB: Q06124#VAR_015605; OMIM: 176876.0009; dbSNP: rs121918460

NCBI 1000 Genomes Browser:

rs121918460

Molecular consequence:

NM_001330437.2:c.184T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.181T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.184T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.184T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Name:: Noonan syndrome (NS)
Synonyms:: Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:: MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000204059	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (May 23, 2014)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 12717436, 15928039, 12325025, 11992261, 17020470, 19352411, 22711529, 16358218, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000204059

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(May 23, 2014)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	9	9	not provided	not provided	not provided	clinical testing

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 (9)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204059.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	9	not provided	not provided	clinical testing	PubMed (9)

Description

The p.Tyr62Asp variant in PTPN11 has been reported in many individuals with the clinical features of Noonan syndrome as well as an individual with Noonan syndro me and juvenile myelomonocytic leukemia (JMML; Tartaglia 2002, Tartaglia 2006, M aheshwari 2002, Bertola 2006, Beneteau 2009, LMM data). This variant has been re ported to have occurred de novo in an affected individual (Maheshwari 2002). In addition, this variant has not been identified in large population studies. In s ummary, the p.Tyr62Asp variant meets our criteria to be classified as pathogenic for Noonan syndrome in an autosomal dominant manner.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		9	not provided	9	not provided

Last Updated: Nov 3, 2024

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