NM_002834.5(PTPN11):c.181G>A (p.Asp61Asn) AND Noonan syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2016
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:: RCV000599619.6

Allele description [Variation Report for NM_002834.5(PTPN11):c.181G>A (p.Asp61Asn)]

NM_002834.5(PTPN11):c.181G>A (p.Asp61Asn)

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.181G>A (p.Asp61Asn)

Other names:

p.D61N:GAT>AAT

HGVS:

NC_000012.12:g.112450361G>A
NG_007459.1:g.36630G>A
NM_001330437.2:c.181G>A
NM_001374625.1:c.178G>A
NM_002834.5:c.181G>AMANE SELECT
NM_080601.3:c.181G>A
NP_001317366.1:p.Asp61Asn
NP_001361554.1:p.Asp60Asn
NP_002825.3:p.Asp61Asn
NP_542168.1:p.Asp61Asn
LRG_614t1:c.181G>A
LRG_614:g.36630G>A
NC_000012.11:g.112888165G>A
NM_001330437.1:c.181G>A
NM_002834.3:c.181G>A
NM_002834.4:c.181G>A
NM_080601.1:c.181G>A
Q06124:p.Asp61Asn

Protein change:

D60N

Links:

UniProtKB: Q06124#VAR_015604; dbSNP: rs397507510

NCBI 1000 Genomes Browser:

rs397507510

Molecular consequence:

NM_001330437.2:c.181G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.181G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.181G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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
SCV000199993	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (May 27, 2016)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 15928039, 14644997, 15842656, 16358218, 23832011, 11992261, 25097206, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000199993

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(May 27, 2016)

germline

clinical testing

PubMed (8)
[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	14	13	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis.

Loh ML, Vattikuti S, Schubbert S, Reynolds MG, Carlson E, Lieuw KH, Cheng JW, Lee CM, Stokoe D, Bonifas JM, Curtiss NP, Gotlib J, Meshinchi S, Le Beau MM, Emanuel PD, Shannon KM.

Blood. 2004 Mar 15;103(6):2325-31. Epub 2003 Nov 26.

PubMed [citation]

PMID:: 14644997

See all PubMed Citations (8)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000199993.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	14	not provided	not provided	clinical testing	PubMed (8)

Description

The p.Asp61Asn variant in PTPN11 has been previously reported in >20 individuals with clinical features of Noonan syndrome (Tartaglia 2002, Tartaglia 2006, Stru llu 2014, LMM data), and at least 4 of whom also had a myoproliferative disorder including juvenile myelomonocytic leukemia (JMML; Loh 2004, Strullu 2014). It i s also absent from large population studies. Computational prediction tools and conservation analysis suggest that the p.Asp61Asn variant may impact the protein , though this information is not predictive enough to determine pathogenicity. I n summary, this variant meets our criteria to be classified as pathogenic for No onan syndrome in an autosomal dominant manner based upon prevalence in affected probands and absence from controls.

#	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		14	not provided	13	not provided

Last Updated: Nov 3, 2024

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