NM_002834.5(PTPN11):c.1507G>C (p.Gly503Arg) AND Noonan Syndrome with Juvenile Myelomonocytic Leukemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 23, 2018
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:: RCV000824750.5

Allele description [Variation Report for NM_002834.5(PTPN11):c.1507G>C (p.Gly503Arg)]

NM_002834.5(PTPN11):c.1507G>C (p.Gly503Arg)

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.1507G>C (p.Gly503Arg)

Other names:

p.G503R:GGG>CGG

HGVS:

NC_000012.12:g.112489083G>C
NG_007459.1:g.75352G>C
NM_001330437.2:c.1519G>C
NM_001374625.1:c.1504G>C
NM_002834.5:c.1507G>CMANE SELECT
NP_001317366.1:p.Gly507Arg
NP_001361554.1:p.Gly502Arg
NP_002825.3:p.Gly503Arg
NP_002825.3:p.Gly503Arg
LRG_614t1:c.1507G>C
LRG_614:g.75352G>C
NC_000012.11:g.112926887G>C
NM_001330437.1:c.1519G>C
NM_002834.3:c.1507G>C
NM_002834.4:c.1507G>C

Protein change:

G502R

Links:

dbSNP: rs397507545

NCBI 1000 Genomes Browser:

rs397507545

Molecular consequence:

NM_001330437.2:c.1519G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.1504G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.1507G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Juvenile myelomonocytic leukemia (JMML)
Synonyms:: LEUKEMIA, JUVENILE MYELOMONOCYTIC, SOMATIC
Identifiers:: MONDO: MONDO:0011908; MedGen: C0349639; Orphanet: 86834; OMIM: 607785; Human Phenotype Ontology: HP:0012209

Name:: Noonan syndrome (NS)
Synonyms:: Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:: MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

Recent activity

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AGENCOURT_11210942 NICHD_XGC_Tad2 Xenopus laevis cDNA clone IMAGE:6873792 5', mR...
AGENCOURT_11210942 NICHD_XGC_Tad2 Xenopus laevis cDNA clone IMAGE:6873792 5', mRNA sequence
gi|29135877|gnl|dbEST|17126448|gb|C 96.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000204060	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Mar 23, 2018)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 12717436, 15928039, 18758896, 15001945, 22465605, 16358218, 12960218, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000204060

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Mar 23, 2018)

germline

clinical testing

PubMed (8)
[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	8	6	not provided	not provided	not provided	clinical testing

Citations

PubMed

Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia.

Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, Hählen K, Hasle H, Licht JD, Gelb BD.

Nat Genet. 2003 Jun;34(2):148-50.

PubMed [citation]

PMID:: 12717436

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 (8)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204060.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	8	not provided	not provided	clinical testing	PubMed (8)

Description

The p.Gly503Arg (due to c.1507G>C or c.1507G>A) variant has previously been repo rted >10 individuals with the clinical features of Noonan syndrome, including at least 2 de novo occurrences (Tartaglia 2003, Sarkozy 2003, Zenker 2004, Kratz 2 005, Lo 2008, Ezquieta 2012, LMM data). This variant has also been reported in i ndividuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML), JMM L, and Noonan syndrome with Hodgkin?s lymphoma (Tartaglia 2003, Lo 2008). It ha s not been identified in large population studies. Three other variants involvin g this codon (p.Gly503Glu, p.Gly503Ala, p.Gly503Val) have been reported as patho genic. Computational prediction tools and conservation analysis suggest that the p.Gly503Arg variant may impact the protein. In summary, this variant meets crit eria to be classified as pathogenic for Noonan syndrome in an autosomal dominant manner. ACMG/AMP Criteria applied: PS4; PM1; PM2; PM6; PP3.

#	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		8	not provided	6	not provided

Last Updated: Oct 13, 2024

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