NM_002834.5(PTPN11):c.174C>A (p.Asn58Lys) AND Noonan syndrome 3

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 25, 2016
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:: RCV000587067.1

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 3 (NS3)
Synonyms:: KRAS-Related Noonan Syndrome
Identifiers:: MONDO: MONDO:0012371; MedGen: C1860991; Orphanet: 648; OMIM: 609942

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000698062	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 25, 2016)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 20954246, 23321623, 22190897, 12634870, 22465605, 16358218, 25914815 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000698062

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 25, 2016)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

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

Citations

PubMed

Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations.

Derbent M, Öncel Y, Tokel K, Varan B, Haberal A, Yazici AC, Legius E, Özbek N.

Am J Med Genet A. 2010 Nov;152A(11):2768-74. doi: 10.1002/ajmg.a.33713.

PubMed [citation]

PMID:: 20954246

Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings.

Croonen EA, Nillesen WM, Stuurman KE, Oudesluijs G, van de Laar IM, Martens L, Ockeloen C, Mathijssen IB, Schepens M, Ruiterkamp-Versteeg M, Scheffer H, Faas BH, van der Burgt I, Yntema HG.

Eur J Hum Genet. 2013 Sep;21(9):936-42. doi: 10.1038/ejhg.2012.285. Epub 2013 Jan 16.

PubMed [citation]

PMID:: 23321623
PMCID:: PMC3746261

See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698062.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

Variant summary: Variant affects a non-conserved nucleotide and results in a replacement of a medium size and polar Asparagine (N) with a large size and basic Lysine (K). 4/4 in silico tools predict the variant to be disease causing. It is absent from the large and broad cohorts of the ExAC project while it was found in several NS patients either as a de novo or as a familiar mutation suggesting pathogenicity. Variants affecting the same amino acid, Asn58His and Asn58Asp, Asn58Tyr have been reported by our laboratory in the pathogenic spectrum suggesting the Asn58 residue to be a mutational hotspot and further supporting a casual outcome for the variant. Furthermore, clinical diagnostic centers classify variant as Pathogenic via ClinVar (without evidence to independently evaluate). Considering all evidence, the variant was classified as Pathogenic.

#	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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