NM_002834.5(PTPN11):c.214G>T (p.Ala72Ser) AND Noonan syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 15, 2014
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:: RCV000157001.18

Allele description [Variation Report for NM_002834.5(PTPN11):c.214G>T (p.Ala72Ser)]

NM_002834.5(PTPN11):c.214G>T (p.Ala72Ser)

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.214G>T (p.Ala72Ser)

Other names:

p.A72S:GCC>TCC

HGVS:

NC_000012.12:g.112450394G>T
NG_007459.1:g.36663G>T
NM_001330437.2:c.214G>T
NM_001374625.1:c.211G>T
NM_002834.5:c.214G>TMANE SELECT
NM_080601.3:c.214G>T
NP_001317366.1:p.Ala72Ser
NP_001361554.1:p.Ala71Ser
NP_002825.3:p.Ala72Ser
NP_542168.1:p.Ala72Ser
LRG_614t1:c.214G>T
LRG_614:g.36663G>T
NC_000012.11:g.112888198G>T
NM_002834.3:c.214G>T
NM_080601.1:c.214G>T
Q06124:p.Ala72Ser
c.214G>T

Protein change:

A71S; ALA72SER

Links:

UniProtKB: Q06124#VAR_015608; OMIM: 176876.0001; dbSNP: rs121918453

NCBI 1000 Genomes Browser:

rs121918453

Molecular consequence:

NM_001330437.2:c.214G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.211G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.214G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.214G>T - 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
SCV000061298	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (May 15, 2014)	germline	clinical testing	PubMed (14) [See all records that cite these PMIDs] 12634870, 12161469, 14974085, 16399795, 16631468, 14961557, 15001945, 16263833, 19737548, 18562489, 17339163, 16358218, 17177198, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061298

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(May 15, 2014)

germline

clinical testing

PubMed (14)
[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	13	12	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome.

Musante L, Kehl HG, Majewski F, Meinecke P, Schweiger S, Gillessen-Kaesbach G, Wieczorek D, Hinkel GK, Tinschert S, Hoeltzenbein M, Ropers HH, Kalscheuer VM.

Eur J Hum Genet. 2003 Feb;11(2):201-6. Erratum in: Eur J Hum Genet. 2003 Jul;11(7):551.

PubMed [citation]

PMID:: 12634870

PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome.

Kosaki K, Suzuki T, Muroya K, Hasegawa T, Sato S, Matsuo N, Kosaki R, Nagai T, Hasegawa Y, Ogata T.

J Clin Endocrinol Metab. 2002 Aug;87(8):3529-33.

PubMed [citation]

PMID:: 12161469

See all PubMed Citations (14)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061298.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	13	not provided	not provided	clinical testing	PubMed (14)

Description

The Ala72Ser variant has been reported in the literature in many individuals wit h clinical features of Noonan syndrome (Zenker 2004, Tartaglia 2006, Kosaki 2002 , Bocchinfuso 2007, Fragale 2004, Hung 2007, Limal 2006, Lo 2009, Martinelli 200 6, Musante 2003, Noordam 2008, Oishi 2006). Other variants at this position (Ala 72Thr, Ala72Val) have been observed as somatic changes in hematologic malignanci es, indicating the importance of this residue in normal function of the protein (Tartaglia 2005). In summary, this variant meets our criteria to be classified a s pathogenic (http://pcpgm.partners.org/LMM).

#	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		13	not provided	12	not provided

Last Updated: Apr 15, 2024

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