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

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

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:
1

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000199998Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Apr 5, 2013)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical 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, Partners HealthCare Personalized Medicine, SCV000199998.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Nov 27, 2021

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