NM_002834.5(PTPN11):c.417G>C (p.Glu139Asp) AND Noonan Syndrome with Juvenile Myelomonocytic Leukemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 7, 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:: RCV000824741.12

Allele description [Variation Report for NM_002834.5(PTPN11):c.417G>C (p.Glu139Asp)]

NM_002834.5(PTPN11):c.417G>C (p.Glu139Asp)

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.417G>C (p.Glu139Asp)

Other names:

p.E139D:GAG>GAC; NM_002834.4(PTPN11):c.417G>C

HGVS:

NC_000012.12:g.112453279G>C
NG_007459.1:g.39548G>C
NM_001330437.2:c.417G>C
NM_001374625.1:c.414G>C
NM_002834.5:c.417G>CMANE SELECT
NM_080601.3:c.417G>C
NP_001317366.1:p.Glu139Asp
NP_001361554.1:p.Glu138Asp
NP_002825.3:p.Glu139Asp
NP_002825.3:p.Glu139Asp
NP_542168.1:p.Glu139Asp
LRG_614t1:c.417G>C
LRG_614:g.39548G>C
LRG_614p1:p.Glu139Asp
NC_000012.11:g.112891083G>C
NM_001330437.1:c.417G>C
NM_002834.3:c.417G>C
NM_002834.4:c.417G>C
Q06124:p.Glu139Asp

Protein change:

E138D

Links:

UniProtKB: Q06124#VAR_015613; dbSNP: rs397507520

NCBI 1000 Genomes Browser:

rs397507520

Molecular consequence:

NM_001330437.2:c.417G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.414G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.417G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.417G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000203936	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Dec 7, 2018)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 17339163, 18372317, 14644997, 11992261, 19737548, 17020470, 19020799, 17361219, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000203936

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Dec 7, 2018)

germline

clinical testing

PubMed (9)
[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	29	26	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational analysis of PTPN11 gene in Taiwanese children with Noonan syndrome.

Hung CS, Lin JL, Lee YJ, Lin SP, Chao MC, Lo FS.

J Formos Med Assoc. 2007 Feb;106(2):169-72.

PubMed [citation]

PMID:: 17339163

Diverse driving forces underlie the invariant occurrence of the T42A, E139D, I282V and T468M SHP2 amino acid substitutions causing Noonan and LEOPARD syndromes.

Martinelli S, Torreri P, Tinti M, Stella L, Bocchinfuso G, Flex E, Grottesi A, Ceccarini M, Palleschi A, Cesareni G, Castagnoli L, Petrucci TC, Gelb BD, Tartaglia M.

Hum Mol Genet. 2008 Jul 1;17(13):2018-29. doi: 10.1093/hmg/ddn099. Epub 2008 Mar 27.

PubMed [citation]

PMID:: 18372317
PMCID:: PMC2900904

See all PubMed Citations (9)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000203936.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	29	not provided	not provided	clinical testing	PubMed (9)

Description

The p.Glu139Asp variant in PTPN11 has been identified in many individuals with c linical features of Noonan syndrome, one individual with clinical features of No onan syndrome and acute lymphoblastic leukemia, and one individual with juvenile myelomonocytic leukemia (Ko 2008, Karow 2007, Tartaglia 2002, Chan 2006, Loh 20 04, Bertola 2006, Hung 2007, Lo 2009, LMM unpublished data). This variant has be en reported to have segregated in familial cases and to have occurred de novo as well. In summary, this variant meets our criteria to be classified as pathogeni c. ACMG/AMP criteria applied: PS4, PM2, PM6, PP2, PP1.

#	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		29	not provided	26	not provided

Last Updated: Nov 10, 2024

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