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NM_002834.5(PTPN11):c.179G>T (p.Gly60Val) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jul 26, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000049228.5

Allele description [Variation Report for NM_002834.5(PTPN11):c.179G>T (p.Gly60Val)]

NM_002834.5(PTPN11):c.179G>T (p.Gly60Val)

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.179G>T (p.Gly60Val)
Other names:
p.G60V
HGVS:
  • NC_000012.12:g.112450359G>T
  • NG_007459.1:g.36628G>T
  • NM_001330437.2:c.179G>T
  • NM_001374625.1:c.176G>T
  • NM_002834.5:c.179G>TMANE SELECT
  • NM_080601.3:c.179G>T
  • NP_001317366.1:p.Gly60Val
  • NP_001361554.1:p.Gly59Val
  • NP_002825.3:p.Gly60Val
  • NP_542168.1:p.Gly60Val
  • LRG_614t1:c.179G>T
  • LRG_614:g.36628G>T
  • NC_000012.11:g.112888163G>T
  • NM_001330437.2:c.179G>T
  • NM_002834.3:c.179G>T
  • NM_080601.1:c.179G>T
  • Q06124:p.Gly60Val
Protein change:
G59V
Links:
UniProtKB: Q06124#VAR_015990; dbSNP: rs397507509
NCBI 1000 Genomes Browser:
rs397507509
Molecular consequence:
  • NM_001330437.2:c.179G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.176G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.179G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.179G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000077242GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Pathogenic
(Sep 7, 2021) 		germlineclinical testing

Citation Link,

SCV004562767ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)		Pathogenic
(Jul 26, 2023) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000077242.15

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 27959697, 32499245, 27923552, 31130284, 18701506, 16358218, 15928039, 27460089, 30050098, 29296745, 32934818, 29493581, 16053901, 9491886, 11992261)

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004562767.1

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

Description

The PTPN11 c.179G>T; p.Gly60Val variant (rs397507509) is reported in the literature in multiple individuals affected with Noonan syndrome (Leach 2019, Monies 2006, Posey 2017). This variant is also reported in ClinVar (Variation ID: 55797) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, other amino acid substitutions at this codon (Ala, Cys, Ser) have been reported in individuals with Noonan syndrome and are considered pathogenic (Bertelloni 2013, Limal 2006). Computational analyses predict that this variant is deleterious (REVEL: 0.931). Based on available information, this variant is considered to be pathogenic. References: Bertelloni S et al. IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene. Hormones (Athens). 2013 Jan-Mar;12(1):86-92. PMID: 23624134. Leach NT et al. Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions. Genet Med. 2019 Feb;21(2):417-425. PMID: 29907801. Limal JM et al. Noonan syndrome: relationships between genotype, growth, and growth factors. J Clin Endocrinol Metab. 2006 Jan;91(1):300-6. PMID: 16263833. Monies D et al. Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population. Am J Hum Genet. 2019 Jun 6;104(6):1182-1201. PMID: 31130284. Posey JE et al. Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation. N Engl J Med. 2017 Jan 5;376(1):21-31. PMID: 27959697.

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

Last Updated: Feb 25, 2025