NM_002834.5(PTPN11):c.235C>A (p.Gln79Lys) AND Noonan syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 28, 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:: RCV000037640.5

Allele description [Variation Report for NM_002834.5(PTPN11):c.235C>A (p.Gln79Lys)]

NM_002834.5(PTPN11):c.235C>A (p.Gln79Lys)

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.235C>A (p.Gln79Lys)

HGVS:

NC_000012.12:g.112450415C>A
NG_007459.1:g.36684C>A
NM_001330437.2:c.235C>A
NM_001374625.1:c.232C>A
NM_002834.5:c.235C>AMANE SELECT
NM_080601.3:c.235C>A
NP_001317366.1:p.Gln79Lys
NP_001361554.1:p.Gln78Lys
NP_002825.3:p.Gln79Lys
NP_542168.1:p.Gln79Lys
LRG_614t1:c.235C>A
LRG_614:g.36684C>A
NC_000012.11:g.112888219C>A
NM_002834.3:c.235C>A
c.235C>A

Protein change:

Q78K

Links:

dbSNP: rs397516803

NCBI 1000 Genomes Browser:

rs397516803

Molecular consequence:

NM_001330437.2:c.235C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.232C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.235C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.235C>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000061302	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Jan 28, 2013)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22848035, 16358218, 12960218, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061302

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Jan 28, 2013)

germline

clinical testing

PubMed (4)
[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	3	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Case report: Noonan syndrome with multiple giant cell lesions and review of the literature.

Karbach J, Coerdt W, Wagner W, Bartsch O.

Am J Med Genet A. 2012 Sep;158A(9):2283-9. doi: 10.1002/ajmg.a.35493. Epub 2012 Jul 27. Review.

PubMed [citation]

PMID:: 22848035

Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease.

Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, Zampino G, Burgt Iv, Palleschi A, Petrucci TC, Sorcini M, Schoch C, Foa R, Emanuel PD, Gelb BD.

Am J Hum Genet. 2006 Feb;78(2):279-90. Epub 2005 Dec 7.

PubMed [citation]

PMID:: 16358218
PMCID:: PMC1380235

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061302.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (4)

Description

The Gln79Lys variant in PTPN11 has been identified by our laboratory in three af fected individuals in from a family with clinical features of Noonan syndrome. W hile this variant has not been reported in the literature, two different amino a cid changes at this position have been reported and identified by our laboratory in many individuals with clinical features of Noonan syndrome (Gln79Arg, Gln79P ro; Karbach 2011, Sarkozy 2003, Tartaglia 2006). At least two of these cases occ urred de novo (Sarkozy 2003). Computational analyses (biochemical amino acid pro perties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong sup port for or against an impact to the protein. In summary, this variant is likely pathogenic based on the presence of other pathogenic variants at this position and the segregation of this variant in family members, though additional studies are required to fully establish its clinical significance.

#	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		3	not provided	1	not provided

Last Updated: Sep 29, 2024

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