NM_002834.5(PTPN11):c.174C>A (p.Asn58Lys) AND Noonan syndrome 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 3, 2022
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:: RCV001358687.4

Allele description [Variation Report for NM_002834.5(PTPN11):c.174C>A (p.Asn58Lys)]

NM_002834.5(PTPN11):c.174C>A (p.Asn58Lys)

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.174C>A (p.Asn58Lys)

Other names:

p.N58K:AAC>AAA

HGVS:

NC_000012.12:g.112450354C>A
NG_007459.1:g.36623C>A
NM_001330437.2:c.174C>A
NM_001374625.1:c.171C>A
NM_002834.5:c.174C>AMANE SELECT
NM_080601.3:c.174C>A
NP_001317366.1:p.Asn58Lys
NP_001361554.1:p.Asn57Lys
NP_002825.3:p.Asn58Lys
NP_542168.1:p.Asn58Lys
LRG_614t1:c.174C>A
LRG_614:g.36623C>A
NC_000012.11:g.112888158C>A
NM_002834.3:c.174C>A
Q06124:p.Asn58Lys
c.174C>A

Protein change:

N57K

Links:

UniProtKB: Q06124#VAR_027184; dbSNP: rs397507506

Molecular consequence:

NM_001330437.2:c.174C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.171C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.174C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.174C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Noonan syndrome 1 (NS1)
Synonyms:: FEMALE PSEUDO-TURNER SYNDROME; TURNER PHENOTYPE WITH NORMAL KARYOTYPE; PTPN11-Related Noonan Syndrome
Identifiers:: MONDO: MONDO:0008104; MedGen: C4551602; Orphanet: 648; OMIM: 163950

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001554497	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34782754, 25741868
SCV007449263	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 3, 2022)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 15928039, 12634870, 16358218, 23321623, 25914815, 22190897, 20954246, 9491886, 16053901, 11992261, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001554497

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

de novo

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV007449263

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 3, 2022)

germline

clinical testing

PubMed (11)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Accelerated genome sequencing with controlled costs for infants in intensive care units: a feasibility study in a French hospital network.

Denommé-Pichon AS, Vitobello A, Olaso R, Ziegler A, Jeanne M, Tran Mau-Them F, Couturier V, Racine C, Isidor B, Poë C, Jouan T, Boland A, Fin B, Bacq-Daian D, Besse C, Garde A, Prost A, Garret P, Tisserant É, Delanne J, Nambot S, Juven A, et al.

Eur J Hum Genet. 2022 May;30(5):567-576. doi: 10.1038/s41431-021-00998-4. Epub 2021 Nov 15.

PubMed [citation]

PMID:: 34782754
PMCID:: PMC9091203

The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease.

Kratz CP, Niemeyer CM, Castleberry RP, Cetin M, Bergsträsser E, Emanuel PD, Hasle H, Kardos G, Klein C, Kojima S, Stary J, Trebo M, Zecca M, Gelb BD, Tartaglia M, Loh ML.

Blood. 2005 Sep 15;106(6):2183-5. Epub 2005 May 31.

PubMed [citation]

PMID:: 15928039
PMCID:: PMC1895140

See all PubMed Citations (12)

Details of each submission

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV001554497.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital, SCV007449263.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

A different nucleotide change resulting in the same amino acid substitution has been reported as pathogenic (ACMG/AMP: PS1; PMIDs:15928039, 12634870, 16358218, 23321623, 25914815, 22190897, 20954246). This variant has been reported at an elevated frequency in affected individuals/in multiple affected individuals in the literature (ACMG/AMP: PS4_Supporting; PMIDs:15928039, 12634870, 16358218, 23321623, 25914815, 22190897, 20954246). This variant is located in a mutational hot spot and/or critical and well-established functional domain (ACMG/AMP: PM1; PMIDs:9491886, 16053901, 11992261). This variant is absent from or present at an exceedingly low frequency in gnomAD, a large-scale control population database (ACMG/AMP: PM2). This variant has been reported to occur de novo in an affected individual in the literature without parental identity confirmed (ACMG/AMP: PM6). This variant occurs in a gene with a low rate of benign missense variation, in which missense alterations are a common mechanism of disease (ACMG/AMP: PP2).

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

Last Updated: Sep 27, 2026

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