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NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp) AND PTPN11-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 17, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV004734537.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp)]

NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp)

Gene:
PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.13
Genomic location:
Preferred name:
NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp)
Other names:
p.E76D:GAG>GAT
HGVS:
  • NC_000012.12:g.112450408G>T
  • NG_007459.1:g.36677G>T
  • NM_001330437.2:c.228G>T
  • NM_001374625.1:c.225G>T
  • NM_002834.5:c.228G>TMANE SELECT
  • NM_080601.3:c.228G>T
  • NP_001317366.1:p.Glu76Asp
  • NP_001361554.1:p.Glu75Asp
  • NP_002825.3:p.Glu76Asp
  • NP_002825.3:p.Glu76Asp
  • NP_542168.1:p.Glu76Asp
  • LRG_614t1:c.228G>T
  • LRG_614:g.36677G>T
  • NC_000012.11:g.112888212G>T
  • NM_001330437.1:c.228G>T
  • NM_002834.3:c.228G>T
  • NM_002834.4:c.228G>T
  • Q06124:p.Glu76Asp
  • c.228G>T
  • p.(Glu76Asp)
Protein change:
E75D
Links:
UniProtKB: Q06124#VAR_015610; dbSNP: rs397507514
NCBI 1000 Genomes Browser:
rs397507514
Molecular consequence:
  • NM_001330437.2:c.228G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.225G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.228G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.228G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
PTPN11-related disorder
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005362203PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Aug 17, 2024) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV005362203.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The PTPN11 c.228G>T variant is predicted to result in the amino acid substitution p.Glu76Asp. This variant has been reported in many individuals with Noonan syndrome (Tartaglia et al. 2006. PubMed ID: 16358218; Table S3, Leach et al. 2019. PubMed ID: 29907801; Table S4, Zhu et al. 2018. PubMed ID: 30029678). Functional studies support this variants pathogenicity (Edouard et al. 2010. PubMed ID: 20308328). This variant has not been reported in a large population database, indicating this variant is rare. In ClinVar, this variant has been interpreted as pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/40502/). An alternate nucleotide substitution resulting in the same missense variant (c.228G>C (p.Glu76Asp)) has been reported as pathogenic (ClinVar ID: 40503). Alternate amino acid substitutions affecting this amino acid (p.Glu76Gln, p.Glu76Ala, p.Glu76Gly, p.Glu76Val) have been interpreted as pathogenic in ClinVar (ClinVar IDs: 181496, 13339, 13338, 13337). This variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 22, 2025