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

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Sep 30, 2021)
Last evaluated:
Feb 29, 2020
Accession:
VCV000040499.8
Variation ID:
40499
Description:
single nucleotide variant
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NM_002834.5(PTPN11):c.211T>C (p.Phe71Leu)

Allele ID
48969
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q24.13
Genomic location
12: 112450391 (GRCh38) GRCh38 UCSC
12: 112888195 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q06124:p.Phe71Leu
NC_000012.11:g.112888195T>C
NC_000012.12:g.112450391T>C
... more HGVS
Protein change
F71L, F70L
Other names
p.F71L:TTT>CTT
Canonical SPDI
NC_000012.12:112450390:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA273215
UniProtKB: Q06124#VAR_015995
dbSNP: rs397507512
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Feb 29, 2020 RCV000033470.9
Likely pathogenic 1 criteria provided, single submitter Apr 5, 2013 RCV000151689.1
Likely pathogenic 1 criteria provided, single submitter Mar 27, 2017 RCV000586528.1
Pathogenic 1 criteria provided, single submitter Jun 11, 2018 RCV000686123.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PTPN11 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
549 563

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Feb 29, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000057375.14
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Likely pathogenic
(Apr 05, 2013)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000199998.5
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (5)
Comment:
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 … (more)
Likely pathogenic
(Mar 27, 2017)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome 3
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698068.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (10)
Comment:
Variant summary: The PTPN11 c.211T>C (p.Phe71Leu) variant located in the N-SH2 domain involves the alteration of a conserved nucleotide and 3/4 in silico tools (SNPs&GO … (more)
Pathogenic
(Jun 11, 2018)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Invitae
Accession: SCV000813626.1
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces phenylalanine with leucine at codon 71 of the PTPN11 protein (p.Phe71Leu). The phenylalanine residue is moderately conserved and there is a … (more)
Pathogenic
(Apr 11, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884431.1
Submitted: (Oct 10, 2018)
Evidence details
Comment:
The PTPN11 c.211T>C; p.Phe71Leu variant (rs397507512) has been reported as a germline variant in multiple individuals with Noonan syndrome (Musante 2003, Strullu 2014), and also … (more)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953193.1
Submitted: (Sep 30, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798140.1
Submitted: (Aug 19, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Clonal and microclonal mutational heterogeneity in high hyperdiploid acute lymphoblastic leukemia. de Smith AJ Oncotarget 2016 PMID: 27683039
Juvenile myelomonocytic leukaemia and Noonan syndrome. Strullu M Journal of medical genetics 2014 PMID: 25097206
The spectrum of somatic mutations in high-risk acute myeloid leukaemia with -7/del(7q). McNerney ME British journal of haematology 2014 PMID: 24931631
PTPN11-associated mutations in the heart: has LEOPARD changed Its RASpots? Lauriol J Trends in cardiovascular medicine 2011 PMID: 22681964
Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Zhang J Blood 2011 PMID: 21680795
High resolution melting analysis for mutation detection for PTPN11 gene: applications of this method for diagnosis of Noonan syndrome. Lo FS Clinica chimica acta; international journal of clinical chemistry 2009 PMID: 19737548
PTPN11 analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings. Lee KA Clinical genetics 2009 PMID: 18759865
The tyrosine phosphatase Shp2 (PTPN11) in cancer. Chan G Cancer metastasis reviews 2008 PMID: 18286234
Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations. Niimi H Leukemia 2006 PMID: 16467864
Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Tartaglia M American journal of human genetics 2006 PMID: 16358218
The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. Kratz CP Blood 2005 PMID: 15928039
Somatic PTPN11 mutations in childhood acute myeloid leukaemia. Tartaglia M British journal of haematology 2005 PMID: 15842656
PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group. Loh ML Leukemia 2004 PMID: 15385933
Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. Loh ML Blood 2004 PMID: 14644997
Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. Musante L European journal of human genetics : EJHG 2003 PMID: 12634870

Text-mined citations for rs397507512...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021