Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_002834.5(PTPN11):c.178G>C (p.Gly60Arg)

Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
First in ClinVar:
Jan 9, 2017
Most recent Submission:
Jun 22, 2021
Last evaluated:
Jun 7, 2021
Variation ID:
single nucleotide variant

NM_002834.5(PTPN11):c.178G>C (p.Gly60Arg)

Allele ID
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
Genomic location
12: 112450358 (GRCh38) GRCh38 UCSC
12: 112888162 (GRCh37) GRCh37 UCSC
Nucleotide Protein Molecular
NM_002834.5:c.178G>C MANE Select NP_002825.3:p.Gly60Arg missense
NM_001330437.2:c.178G>C NP_001317366.1:p.Gly60Arg missense
NM_001374625.1:c.175G>C NP_001361554.1:p.Gly59Arg missense
... more HGVS
Protein change
G60R, G59R
Other names
Canonical SPDI
Functional consequence
Global minor allele frequency (GMAF)

Allele frequency
ClinGen: CA16042862
dbSNP: rs397507507

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Mar 6, 2015 RCV000413720.1
Likely pathogenic 1 criteria provided, single submitter Jun 7, 2021 RCV001201204.2
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
810 824

Submitted interpretations and evidence

(Last evaluated)
Review status
(Assertion criteria)
Submitter More information
(Mar 06, 2015)
criteria provided, single submitter
Method: clinical testing
Not Provided
Affected status: yes
Allele origin: germline
Accession: SCV000490934.1
First in ClinVar: Jan 09, 2017
Last updated: Jan 09, 2017
The G60R variant has been reported previously is association with juvenile myelomonocytic leukemia (Loh et al., 2004). The G60R variant was not observed in approximately … (more)
Likely pathogenic
(Jun 07, 2021)
criteria provided, single submitter
Method: clinical testing
Affected status: unknown
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001372285.2
First in ClinVar: Jul 16, 2020
Last updated: Jun 22, 2021
PubMed (14)
Variant summary: PTPN11 c.178G>C (p.Gly60Arg) results in a non-conservative amino acid change located in the SH2 domain (IPR000980) of the encoded protein sequence. Five of … (more)

Functional evidence

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

Title Author Journal Year Link
Systematic Functional Annotation of Somatic Mutations in Cancer. Ng PK Cancer cell 2018 PMID: 29533785
Integrated molecular profiling of juvenile myelomonocytic leukemia. Murakami N Blood 2018 PMID: 29437595
Genomic Classification and Prognosis in Acute Myeloid Leukemia. Papaemmanuil E The New England journal of medicine 2016 PMID: 27276561
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Arber DA Blood 2016 PMID: 27069254
The genomic landscape of juvenile myelomonocytic leukemia. Stieglitz E Nature genetics 2015 PMID: 26457647
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
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

Text-mined citations for rs397507507...

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 Jun 11, 2022