NM_002834.5(PTPN11):c.211T>C (p.Phe71Leu) AND Noonan syndrome

Clinical significance:Likely pathogenic (Last evaluated: Apr 5, 2013)
Review status:1 star out of maximum of 4 stars
criteria provided, single submitter

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Based on:: 1 submission [Details]
Record status:: current
Accession:: RCV000151689.4

Allele description [Variation Report for NM_002834.5(PTPN11):c.211T>C (p.Phe71Leu)]

NM_002834.5(PTPN11):c.211T>C (p.Phe71Leu)

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.211T>C (p.Phe71Leu)

Other names:

p.F71L:TTT>CTT

HGVS:

NC_000012.12:g.112450391T>C
NG_007459.1:g.36660T>C
NM_001330437.2:c.211T>C
NM_001374625.1:c.208T>C
NM_002834.5:c.211T>CMANE SELECT
NM_080601.3:c.211T>C
NP_001317366.1:p.Phe71Leu
NP_001361554.1:p.Phe70Leu
NP_002825.3:p.Phe71Leu
NP_542168.1:p.Phe71Leu
LRG_614t1:c.211T>C
LRG_614:g.36660T>C
NC_000012.11:g.112888195T>C
NM_002834.3:c.211T>C
Q06124:p.Phe71Leu

Protein change:

F70L

Links:

UniProtKB: Q06124#VAR_015995; dbSNP: rs397507512

NCBI 1000 Genomes Browser:

rs397507512

Molecular consequence:

NM_001330437.2:c.211T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.208T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.211T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.211T>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
SCV000199998	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter LMM Criteria	Likely pathogenic (Apr 5, 2013)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16358218, 18286234, 15842656, 15385933, 12634870, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000199998

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

LMM Criteria

Likely pathogenic
(Apr 5, 2013)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

Help

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease.

Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, Zampino G, Burgt Iv, Palleschi A, Petrucci TC, Sorcini M, Schoch C, Foa R, Emanuel PD, Gelb BD.

Am J Hum Genet. 2006 Feb;78(2):279-90. Epub 2005 Dec 7.

PubMed [citation]

PMID:: 16358218
PMCID:: PMC1380235

The tyrosine phosphatase Shp2 (PTPN11) in cancer.

Chan G, Kalaitzidis D, Neel BG.

Cancer Metastasis Rev. 2008 Jun;27(2):179-92. doi: 10.1007/s10555-008-9126-y. Review.

PubMed [citation]

PMID:: 18286234

See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000199998.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (6)

Description

The Phe71Leu variant in PTPN11 has not been seen before in our laboratory; howev er it has been reported in the literature in clinical features of Noonan syndrom e and pediatric acute myeloid leukemia (AML; Musante 2003, Loh 2004, Chan 2006). The Phe71Leu variant has not been identified in large European American and Afr ican American populations by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS/). This variant has also been identified as an acquired somati c mutation in patients with hematological malignancies (Tartaglia 2006, Tartagli a 2005, Loh 2004, Chan 2006). The majority of identified pathogenic variants in the PTPN11 gene are located in exon 3 and involve the amino acids preceding and following the Phe71 residue, affect the N-SH2 domain, and are gain-of-function/a ctivating variants. Computational analyses (biochemical amino acid properties, c onservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for o r against an impact to the protein. In summary, this variant is likely pathogeni c, though additional studies are required to fully establish its clinical signif icance.

#	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		1	not provided	1	not provided

Last Updated: Mar 18, 2023

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