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NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp) AND PTPN11-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 26, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV004532340.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)]

NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)

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.184T>G (p.Tyr62Asp)
Other names:
p.Y62D:TAC>GAC
HGVS:
  • NC_000012.12:g.112450364T>G
  • NG_007459.1:g.36633T>G
  • NM_001330437.2:c.184T>G
  • NM_001374625.1:c.181T>G
  • NM_002834.5:c.184T>GMANE SELECT
  • NM_080601.3:c.184T>G
  • NP_001317366.1:p.Tyr62Asp
  • NP_001317366.1:p.Tyr62Asp
  • NP_001361554.1:p.Tyr61Asp
  • NP_002825.3:p.Tyr62Asp
  • NP_002825.3:p.Tyr62Asp
  • NP_542168.1:p.Tyr62Asp
  • LRG_614t1:c.184T>G
  • LRG_614:g.36633T>G
  • LRG_614p1:p.Tyr62Asp
  • NC_000012.11:g.112888168T>G
  • NM_001330437.1:c.184T>G
  • NM_002834.3:c.184T>G
  • NM_002834.4(PTPN11):c.184T>G
  • NM_002834.4:c.184T>G
  • Q06124:p.Tyr62Asp
Protein change:
Y61D; TYR62ASP
Links:
UniProtKB: Q06124#VAR_015605; OMIM: 176876.0009; dbSNP: rs121918460
NCBI 1000 Genomes Browser:
rs121918460
Molecular consequence:
  • NM_001330437.2:c.184T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.181T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.184T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.184T>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
SCV004120665PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 26, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004120665.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The PTPN11 c.184T>G variant is predicted to result in the amino acid substitution p.Tyr62Asp. This variant has been reported in multiple individuals with Noonan syndrome with multiple cases where the variant arose de novo (see for example - Tartaglia et al. 2002. PubMed ID: 11992261; Szot et al. 2018. PubMed ID: 29555671). Pathogenic variants in PTPN11 act in a gain-of-function manner by causing an upregulation of the RAS pathway. Consistent with this mechanism, functional studies demonstrated this variant leads to elevated levels of ERK phosphorylation (Martinelli et al. 2012. PubMed ID: 22711529). Additionally, different missense variants affecting this residue (p.Tyr62Asn and p.Tyr62Cys) have been reported as pathogenic (Tartaglia et al. 2006. PubMed ID: 16358218; Jongmans et al. 2011. PubMed ID: 21407260). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.

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

Last Updated: Nov 3, 2024