NM_002834.5(PTPN11):c.179G>C (p.Gly60Ala) AND Noonan syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 9, 2015
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:: RCV000037631.6

Allele description [Variation Report for NM_002834.5(PTPN11):c.179G>C (p.Gly60Ala)]

NM_002834.5(PTPN11):c.179G>C (p.Gly60Ala)

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>C (p.Gly60Ala)

HGVS:

NC_000012.12:g.112450359G>C
NG_007459.1:g.36628G>C
NM_001330437.2:c.179G>C
NM_001374625.1:c.176G>C
NM_002834.5:c.179G>CMANE SELECT
NM_080601.3:c.179G>C
NP_001317366.1:p.Gly60Ala
NP_001361554.1:p.Gly59Ala
NP_002825.3:p.Gly60Ala
NP_002825.3:p.Gly60Ala
NP_542168.1:p.Gly60Ala
LRG_614t1:c.179G>C
LRG_614:g.36628G>C
NC_000012.11:g.112888163G>C
NM_002834.3:c.179G>C
NM_002834.4:c.179G>C
Q06124:p.Gly60Ala
c.179G>C
p.(Gly60Ala)

Protein change:

G59A

Links:

UniProtKB: Q06124#VAR_015602; dbSNP: rs397507509

NCBI 1000 Genomes Browser:

rs397507509

Molecular consequence:

NM_001330437.2:c.179G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.176G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.179G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.179G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Noonan syndrome (NS)
Synonyms:: Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:: MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000061293	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Jul 9, 2015)	germline	clinical testing	PubMed (15) [See all records that cite these PMIDs] 11992261, 16358218, 17020470, 14644997, 15928039, 24039098, 16643459, 16263833, 17053061, 18328949, 18562489, 21407260, 15985475, 17546245, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061293

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Jul 9, 2015)

germline

clinical testing

PubMed (15)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	5	4	not provided	not provided	not provided	clinical testing

Citations

PubMed

PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.

Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD.

Am J Hum Genet. 2002 Jun;70(6):1555-63. Epub 2002 May 1.

PubMed [citation]

PMID:: 11992261
PMCID:: PMC379142

Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease.

Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, Zampino G, Burgt Iv, Palleschi A, Petrucci TC, Sorcini M, Schoch C, Foa R, Emanuel PD, Gelb BD.

Am J Hum Genet. 2006 Feb;78(2):279-90. Epub 2005 Dec 7.

PubMed [citation]

PMID:: 16358218
PMCID:: PMC1380235

See all PubMed Citations (15)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061293.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (15)

Description

The p.Gly60Ala variant has been reported in >20 individuals with clinical featur es of Noonan syndrome (Tartaglia 2002, Binder 2005, Bertola 2006, Limal 2006, Ta rtaglia 2006, Roti 2006, Mutesa 2008, Noordam 2008, Jongmans 2011, Ross 2014, LM M unpublished data) but not identified in large population studies. This variant occurred de novo in at least one of the affected individuals (Roti 2006). In ad dition, this variant has been reported in two individuals with clinical features of Noonan syndrome and a central nervous system tumor (neuroblastoma, Mutesa 20 08; dysembryoplastic neuroepithelia tumor, Jongmans 2011) and as a somatic chang e in AML (Loh 2004). In summary, this variant meets our criteria to be classifie d as pathogenic for Noonan syndrome in an autosomal dominant manner based on its frequency in affected individuals, de novo occurrence, and absence from control s.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		5	not provided	4	not provided

Last Updated: Oct 20, 2024

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