NC_000012.12:g.112450397_112450398delinsCT AND Noonan syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 2, 2013
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:: RCV000037637.5

Allele description [Variation Report for NC_000012.12:g.112450397_112450398delinsCT]

NC_000012.12:g.112450397_112450398delinsCT

Gene:

PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

12q24.13

Genomic location:

Preferred name:

NC_000012.12:g.112450397_112450398delinsCT

HGVS:

NC_000012.12:g.112450397_112450398delinsCT
NG_007459.1:g.36666_36667delinsCT
NM_001330437.2:c.217_218delinsCT
NM_001374625.1:c.214_215delinsCT
NM_002834.5:c.217_218delinsCTMANE SELECT
NM_080601.3:c.217_218delinsCT
NP_001317366.1:p.Thr73Leu
NP_001361554.1:p.Thr72Leu
NP_002825.3:p.Thr73Leu
NP_542168.1:p.Thr73Leu
LRG_614:g.36666_36667delinsCT
NC_000012.11:g.112888201_112888202delinsCT
NM_002834.5:c.217_218delinsCT
c.217_218delinsCT

Protein change:

T72L

Links:

dbSNP: rs397516802

NCBI 1000 Genomes Browser:

rs397516802

Observations:

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
SCV000061299	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Apr 2, 2013)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22465605, 12717436, 16358218, 15928039, 15723289, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061299

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Apr 2, 2013)

germline

clinical testing

PubMed (6)
[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	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy.

Ezquieta B, Santomé JL, Carcavilla A, Guillén-Navarro E, Pérez-Aytés A, Sánchez del Pozo J, García-Miñaur S, Castillo E, Alonso M, Vendrell T, Santana A, Maroto E, Galbis L.

Rev Esp Cardiol (Engl Ed). 2012 May;65(5):447-55. doi: 10.1016/j.recesp.2011.12.016. Epub 2012 Mar 31. English, Spanish.

PubMed [citation]

PMID:: 22465605

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

See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061299.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (6)

Description

The Thr73Leu variant in PTPN11 has previously been reported in the literature in one individual with clinical features of Noonan syndrome where it was reported to have occurred de novo (Ezquieta 2012). This variant was not identified in ei ther parent of this individual and therefore likely occurred de novo, assuming t hat non-medical explanations including alternate paternity or undisclosed adopti on have been ruled out In addition, a different amino acid change at this locati on (Thr73Ile) has previously been reported in the literature in many individuals with Noonan syndrome and Noonan syndrome with Juvenile myelomonocytic leukemia or myelodysplasia (Tartaglia 2003, Kratz 2005, Tartaglia 2006, Jongmans 2005) an d is classified as pathogenic in our laboratory. The evidence above taken togeth er supports that this variant is disease causing and responsible for Noonan synd rome and possibly Juvenile myelomonocytic leukemia or myelodysplasia in this ind ividual. In summary, this variant meets our criteria to be classified as pathoge nic (http://pcpgm.partners.org/LMM).

#	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		1	not provided	1	not provided

Last Updated: Oct 8, 2024

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