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NM_002834.5(PTPN11):c.214G>A (p.Ala72Thr)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
10 (Most recent: Sep 30, 2021)
Last evaluated:
Nov 7, 2019
Accession:
VCV000177754.9
Variation ID:
177754
Description:
single nucleotide variant
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NM_002834.5(PTPN11):c.214G>A (p.Ala72Thr)

Allele ID
175540
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q24.13
Genomic location
12: 112450394 (GRCh38) GRCh38 UCSC
12: 112888198 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q06124:p.Ala72Thr
LRG_614:g.36663G>A
LRG_614t1:c.214G>A
... more HGVS
Protein change
A72T, A71T
Other names
-
Canonical SPDI
NC_000012.12:112450393:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
UniProtKB: Q06124#VAR_015996
dbSNP: rs121918453
ClinGen: CA180706
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Jul 29, 2019 RCV000154367.5
Pathogenic 3 criteria provided, single submitter Nov 7, 2019 RCV000680626.4
Likely pathogenic 1 criteria provided, single submitter Feb 11, 2015 RCV000824740.1
Pathogenic 1 criteria provided, single submitter Mar 27, 2018 RCV000995620.2
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000417864.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000425277.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000443279.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000435950.1
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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
Likely pathogenic
(Feb 11, 2015)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome
Juvenile myelomonocytic leukemia
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000204031.5
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (5)
Comment:
The p.Ala72Thr variant in PTPN11 has been identified by our laboratory as a de n ovo occurrence in one fetus with an increased NT measurement. … (more)
Pathogenic
(Jul 29, 2019)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918109.2
Submitted: (Sep 24, 2019)
Evidence details
Publications
PubMed (13)
Comment:
Variant summary: PTPN11 c.214G>A (p.Ala72Thr) results in a non-conservative amino acid change located in the SH2 domain of the encoded protein sequence. Five of five … (more)
Pathogenic
(Mar 27, 2018)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome 1
(Autosomal dominant inheritance)
Allele origin: de novo
Institute of Human Genetics, Klinikum rechts der Isar
Accession: SCV001149899.1
Submitted: (Jan 21, 2020)
Evidence details
Pathogenic
(Nov 07, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000808069.1
Submitted: (Sep 24, 2021)
Evidence details
Comment:
Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This … (more)
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Neuroblastoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000507235.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Acute myeloid leukemia
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000507232.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Neoplasm of brain
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000507233.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Chronic lymphatic leukemia
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000507234.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely 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: SCV001952190.1
Submitted: (Sep 30, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001964020.1
Submitted: (Sep 21, 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
Lessons from exome sequencing in prenatally diagnosed heart defects: A basis for prenatal testing. Westphal DS Clinical genetics 2019 PMID: 30868567
Juvenile myelomonocytic leukemia-associated variants are associated with neo-natal lethal Noonan syndrome. Mason-Suares H European journal of human genetics : EJHG 2017 PMID: 28098151
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Arber DA Blood 2016 PMID: 27069254
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. Chang MT Nature biotechnology 2016 PMID: 26619011
Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia. Stieglitz E Blood 2015 PMID: 25395418
Juvenile myelomonocytic leukaemia and Noonan syndrome. Strullu M Journal of medical genetics 2014 PMID: 25097206
Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis. Chan G Blood 2009 PMID: 19179468
Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia. Yoshida N Pediatric research 2009 PMID: 19047918
Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD. Hou HA Leukemia 2008 PMID: 17972951
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
Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Mohi MG Cancer cell 2005 PMID: 15710330
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
Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Tartaglia M Nature genetics 2003 PMID: 12717436
http://docm.genome.wustl.edu/variants/ENST00000351677:c.214G>A - - - -

Text-mined citations for rs121918453...

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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