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NM_002834.5(PTPN11):c.155C>T (p.Thr52Ile)

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Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
6
First in ClinVar:
May 29, 2016
Most recent Submission:
Mar 4, 2023
Last evaluated:
Apr 3, 2017
Accession:
VCV000040484.16
Variation ID:
40484
Description:
single nucleotide variant
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NM_002834.5(PTPN11):c.155C>T (p.Thr52Ile)

Allele ID
48954
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q24.13
Genomic location
12: 112450335 (GRCh38) GRCh38 UCSC
12: 112888139 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_002834.5:c.155C>T MANE Select NP_002825.3:p.Thr52Ile missense
NM_001330437.2:c.155C>T NP_001317366.1:p.Thr52Ile missense
NM_001374625.1:c.152C>T NP_001361554.1:p.Thr51Ile missense
... more HGVS
Protein change
T52I, T51I
Other names
p.T52I:ACC>ATC
NM_002834.4(PTPN11):c.155C>T
Canonical SPDI
NC_000012.12:112450334:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA261555
dbSNP: rs397507503
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 3 reviewed by expert panel Apr 3, 2017 RCV000037621.10
Uncertain significance 1 criteria provided, single submitter Apr 28, 2022 RCV000033452.8
Likely pathogenic 1 criteria provided, single submitter Dec 19, 2021 RCV000809051.3
Likely pathogenic 1 criteria provided, single submitter Sep 27, 2022 RCV002287349.2
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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
808 822

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter More information
Likely pathogenic
(Apr 03, 2017)
reviewed by expert panel
Method: curation
Noonan syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin: germline
ClinGen RASopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000616407.4
First in ClinVar: Dec 19, 2017
Last updated: Dec 11, 2022
Other databases
https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/c650daaa-d00c-411a-9439-fe0b0570e53e
Comment:
The c.155C>T (p.Thr52Ile) variant in PTPN11 has been identified in at least 5 independent occurrences in patients with a RASopathy (PS4_Moderate; PMID: 22465605, 25804457, GeneDx, … (more)
Likely pathogenic
(Feb 11, 2016)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome
(Autosomal dominant inheritance)
Affected status: not provided
Allele origin: germline
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061283.6
First in ClinVar: May 03, 2013
Last updated: Aug 26, 2019
Publications:
PubMed (1)
PubMed: 22465605
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Number of individuals with the variant: 2
Likely pathogenic
(Sep 27, 2022)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin: germline
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin
Additional submitter:
CUBI - Core Unit Bioinformatics,Berlin Institute of Health
Accession: SCV002578163.1
First in ClinVar: Oct 08, 2022
Last updated: Oct 08, 2022
Clinical Features:
Short stature (present) , Patent ductus arteriosus (present) , Abnormal pulmonary valve morphology (present) , Global developmental delay (present)
Zygosity: 1 Single Heterozygote
Sex: female
Tissue: Blood
Likely pathogenic
(Dec 19, 2021)
criteria provided, single submitter
Method: clinical testing
RASopathy
Affected status: unknown
Allele origin: germline
Invitae
Accession: SCV000949188.3
First in ClinVar: Aug 14, 2019
Last updated: Feb 07, 2023
Publications:
PubMed (2)
PubMed: 2246560525804457
Comment:
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 52 of the PTPN11 protein (p.Thr52Ile). … (more)
Uncertain significance
(Apr 28, 2022)
criteria provided, single submitter
Method: clinical testing
Not Provided
Affected status: yes
Allele origin: germline
GeneDx
Accession: SCV000057357.14
First in ClinVar: Apr 04, 2013
Last updated: Mar 04, 2023
Comment:
Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant … (more)
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
Noonan syndrome
Affected status: yes
Allele origin: unknown
Service de Génétique Moléculaire,Hôpital Robert Debré
Accession: SCV001438499.1
First in ClinVar: Oct 23, 2020
Last updated: Oct 23, 2020

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
Novel mutations in PTPN11 gene in two girls with Noonan syndrome phenotype. Gulec EY International journal of cardiology 2015 PMID: 25804457
Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy. Ezquieta B Revista espanola de cardiologia (English ed.) 2012 PMID: 22465605
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/c650daaa-d00c-411a-9439-fe0b0570e53e - - - -

Text-mined citations for rs397507503...

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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 Mar 05, 2023