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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 28, 2021
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:: RCV000037629.6

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

NCBI 1000 Genomes Browser:

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 (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
SCV000061291	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 28, 2021)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 15928039, 12634870, 16358218, 23321623, 22465605, 26633542, 33811550, 28911804, 29212898, 29907801, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061291

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 28, 2021)

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

Citations

PubMed

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

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

See all PubMed Citations (11)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061291.7

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

Description

The p.Asn58Lys (c.174C>A) variant in PTPN11 has been reported in at least six individuals with Noonan syndrome and segregated with disease in one affected family member (Chan 2006, Miller 2017 PMID: 29212898, Sublett 2017 PMID: 28911804, D'Amico 2021 PMID: 33811550, LMM data). It has also been reported in one individual with multiple congenital anomalies (Retterer 2015 PMID:26633542). It was absent from large population studies, but has been reported in ClinVar (Variation ID 40488). Another variant resulting in the same amino acid change (c.174C>G) and two additional variants involving this codon (p.Asn58Asp and p.Asn58His) have been identified in individuals with Noonan syndrome and are classified as pathogenic by this laboratory. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Noonan syndrome. ACMG/AMP Criteria applied: PS1, PS4, PM5_Strong, PM2_Supporting.

#	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 29, 2024

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