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NM_002834.5(PTPN11):c.182A>G (p.Asp61Gly) AND PTPN11-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 18, 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:
RCV004532341.3

Allele description [Variation Report for NM_002834.5(PTPN11):c.182A>G (p.Asp61Gly)]

NM_002834.5(PTPN11):c.182A>G (p.Asp61Gly)

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.182A>G (p.Asp61Gly)
Other names:
p.D61G:GAT>GGT
HGVS:
  • NC_000012.12:g.112450362A>G
  • NG_007459.1:g.36631A>G
  • NM_001330437.2:c.182A>G
  • NM_001374625.1:c.179A>G
  • NM_002834.5:c.182A>GMANE SELECT
  • NM_080601.3:c.182A>G
  • NP_001317366.1:p.Asp61Gly
  • NP_001361554.1:p.Asp60Gly
  • NP_002825.3:p.Asp61Gly
  • NP_002825.3:p.Asp61Gly
  • NP_542168.1:p.Asp61Gly
  • LRG_614t1:c.182A>G
  • LRG_614:g.36631A>G
  • LRG_614p1:p.Asp61Gly
  • NC_000012.11:g.112888166A>G
  • NM_002834.3:c.182A>G
  • NM_002834.4:c.182A>G
  • Q06124:p.Asp61Gly
Protein change:
D60G; ASP61GLY
Links:
UniProtKB: Q06124#VAR_015603; OMIM: 176876.0010; dbSNP: rs121918461
NCBI 1000 Genomes Browser:
rs121918461
Molecular consequence:
  • NM_001330437.2:c.182A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.179A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.182A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.182A>G - 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
SCV004721419PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Aug 18, 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, SCV004721419.2

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

Description

The PTPN11 c.182A>G variant is predicted to result in the amino acid substitution p.Asp61Gly. This variant has been repeatedly reported in individuals with Noonan syndrome and is one of the most common pathogenic variants in PTPN11 (see for example Tartaglia et al 2001. PubMed ID: 11704759). In at least two individuals it was reported as a de novo event (Croonen et al. 2013. PubMed ID: 23321623; Joyce et al. 2015. PubMed ID: 26242988). In vitro functional studies and knock-in mouse models are consistent with this variant disrupting normal protein function (Araki et al. 2004. PubMed ID: 15273746; Keilhack et al. 2005. PubMed ID: 15987685; Serra-Nédélec. 2012. PubMed ID: 22371576). This variant has been interpreted as pathogenic by multiple labs in ClinVar. Additionally, different amino acid substitutions (p.Asp61Asn, p.Asp61His, p.Asp61Ala, p.Asp61Val) affecting the same amino acid have been reported as pathogenic (ClinVar IDs: 40495, 40494, 179221, 40496). This variant is interpreted as pathogenic.

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

Last Updated: Nov 3, 2024