NM_002834.5(PTPN11):c.228G>C (p.Glu76Asp) AND Noonan syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 5, 2011
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:: RCV000037638.5

Allele description [Variation Report for NM_002834.5(PTPN11):c.228G>C (p.Glu76Asp)]

NM_002834.5(PTPN11):c.228G>C (p.Glu76Asp)

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.228G>C (p.Glu76Asp)

Other names:

p.E76D:GAG>GAC

HGVS:

NC_000012.12:g.112450408G>C
NG_007459.1:g.36677G>C
NM_001330437.2:c.228G>C
NM_001374625.1:c.225G>C
NM_002834.5:c.228G>CMANE SELECT
NM_080601.3:c.228G>C
NP_001317366.1:p.Glu76Asp
NP_001361554.1:p.Glu75Asp
NP_002825.3:p.Glu76Asp
NP_542168.1:p.Glu76Asp
LRG_614t1:c.228G>C
LRG_614:g.36677G>C
NC_000012.11:g.112888212G>C
NM_002834.3:c.228G>C
Q06124:p.Glu76Asp
c.228G>C

Protein change:

E75D

Links:

UniProtKB: Q06124#VAR_015610; dbSNP: rs397507514

NCBI 1000 Genomes Browser:

rs397507514

Molecular consequence:

NM_001330437.2:c.228G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.225G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.228G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.228G>C - 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
SCV000061300	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Oct 5, 2011)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15928039, 11704759, 16358218, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061300

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Oct 5, 2011)

germline

clinical testing

PubMed (4)
[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	3	3	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, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome.

Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD.

Nat Genet. 2001 Dec;29(4):465-8. Erratum in: Nat Genet 2001 Dec;29(4):491. Nat Genet 2002 Jan;30(1):123.

PubMed [citation]

PMID:: 11704759

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061300.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (4)

Description

The Glu76Asp variant has been reported in at least 7 individuals with clinical f eatures of Noonan syndrome (Tartaglia 2006, Tartaglia 2001). Therefore, this var iant is highly likely to be pathogenic. The presence of a heterozygous pathogeni c variant in PTPN11 is consistent with a diagnosis of Noonan syndrome but this i nformation should be reconciled with the complete clinical history of this indiv idual.

#	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		3	not provided	3	not provided

Last Updated: Sep 29, 2024

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