NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser) AND Noonan syndrome

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Dec 3, 2015
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:: RCV000037669.21

Allele description [Variation Report for NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)]

NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)

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.923A>G (p.Asn308Ser)

Other names:

p.N308S:AAT>AGT

HGVS:

NC_000012.12:g.112477720A>G
NG_007459.1:g.63989A>G
NM_001330437.2:c.923A>G
NM_001374625.1:c.920A>G
NM_002834.5:c.923A>GMANE SELECT
NM_080601.3:c.923A>G
NP_001317366.1:p.Asn308Ser
NP_001361554.1:p.Asn307Ser
NP_002825.3:p.Asn308Ser
NP_542168.1:p.Asn308Ser
LRG_614t1:c.923A>G
LRG_614:g.63989A>G
NC_000012.11:g.112915524A>G
NM_001330437.2:c.923A>G
NM_002834.1:c.923A>G
NM_002834.3:c.923A>G
NM_002834.4:c.923A>G
NM_080601.1:c.923A>G
Q06124:p.Asn308Ser
c.923A>G
p.(Asn308Ser)
p.ASN308SER

Protein change:

N307S; ASN308SER

Links:

UniProtKB: Q06124#VAR_015618; OMIM: 176876.0004; dbSNP: rs121918455

NCBI 1000 Genomes Browser:

rs121918455

Molecular consequence:

NM_001330437.2:c.923A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.920A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.923A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.923A>G - 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
SCV000061331	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Sep 13, 2013)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16124853, 12960218, 11992261, 19077116, 19020799, 24033266
SCV000264159	Blueprint Genetics	criteria provided, single submitter (Variant Classification)	Pathogenic (Dec 3, 2015)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11992261, 22190897, 20718194 Citation Link,
SCV000292262	Donald Williams Parsons Laboratory, Baylor College of Medicine - CSER-BASIC3 See additional submitters Sharon E. Plon Laboratory, Baylor College of Medicine	criteria provided, single submitter (Parsons' et. al 2016)	Pathogenic	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26822237, 27626068
SCV000805103	Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	no assertion criteria provided	Pathogenic (Mar 8, 2017)	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	48	45	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
African American	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Noonan syndrome and related disorders: genetics and pathogenesis.

Tartaglia M, Gelb BD.

Annu Rev Genomics Hum Genet. 2005;6:45-68. Review.

PubMed [citation]

PMID:: 16124853

Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes.

Sarkozy A, Conti E, Seripa D, Digilio MC, Grifone N, Tandoi C, Fazio VM, Di Ciommo V, Marino B, Pizzuti A, Dallapiccola B.

J Med Genet. 2003 Sep;40(9):704-8. No abstract available.

PubMed [citation]

PMID:: 12960218
PMCID:: PMC1735592

See all PubMed Citations (10)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061331.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	48	not provided	not provided	clinical testing	PubMed (6)

Description

The p.Asn308Ser variant has previously been associated with the clinical feature s of Noonan syndrome and Noonan syndrome associated with multiple giant-cell les ions in bone (Ko 2008, Tartaglia 2002, Pierpont 2009, Sarkozy 2003, Tartaglia 20 05). This variant has been observed to have occurred de novo in sporadic cases a nd to segregate with clinical features in familial cases. Variants affecting pos ition 308 (p.Asn308Ser and p.Asn308Asp) are the most frequently identified patho genic PTPN11 mutations in individuals with clinical features of Noonan syndrome in our laboratory. In summary, this variant meets our criteria to be classified as pathogenic (http://www.partners.org/personalizedmedicine/LMM) based upon seg regation studies, de novo occurrence, and absence from controls.

#	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		48	not provided	45	not provided

From Blueprint Genetics, SCV000264159.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

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

From Donald Williams Parsons Laboratory, Baylor College of Medicine - CSER-BASIC3, SCV000292262.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	African American	1	not provided	not provided	clinical testing	PubMed (2)

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

From Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital, SCV000805103.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

Last Updated: Nov 3, 2024

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