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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:
5 (Most recent: Sep 25, 2021)
Last evaluated:
Apr 3, 2017
Accession:
VCV000040484.6
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
LRG_614t1:c.155C>T
NC_000012.11:g.112888139C>T
NC_000012.12:g.112450335C>T
... 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 RCV000037621.6
Uncertain significance 1 criteria provided, single submitter Jun 15, 2020 RCV000033452.6
Uncertain significance 1 criteria provided, single submitter Aug 17, 2018 RCV000809051.1
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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
(Apr 03, 2017)
reviewed by expert panel
Method: curation
Noonan syndrome
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen RASopathy Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000616407.3
Submitted: (Feb 25, 2019)
Evidence details
Other databases
https://erepo.clinicalgenome.org…
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)
Uncertain significance
(Aug 17, 2018)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Invitae
Accession: SCV000949188.1
Submitted: (Mar 28, 2019)
Evidence details
Comment:
This sequence change replaces threonine with isoleucine at codon 52 of the PTPN11 protein (p.Thr52Ile). The threonine residue is moderately conserved and there is a … (more)
Likely pathogenic
(Feb 11, 2016)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000061283.6
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (1)
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Uncertain significance
(Jun 15, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000057357.12
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico … (more)
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
Noonan syndrome
Allele origin: unknown
Service de Génétique Moléculaire,Hôpital Robert Debré
Accession: SCV001438499.1
Submitted: (Mar 26, 2020)
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
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 Nov 27, 2021