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NM_002834.5(PTPN11):c.1505C>T (p.Ser502Leu) AND Noonan syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 15, 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:
RCV000037619.14

Allele description [Variation Report for NM_002834.5(PTPN11):c.1505C>T (p.Ser502Leu)]

NM_002834.5(PTPN11):c.1505C>T (p.Ser502Leu)

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.1505C>T (p.Ser502Leu)
Other names:
p.S502L:TCA>TTA
HGVS:
  • NC_000012.12:g.112489081C>T
  • NG_007459.1:g.75350C>T
  • NM_001330437.2:c.1517C>T
  • NM_001374625.1:c.1502C>T
  • NM_002834.5:c.1505C>TMANE SELECT
  • NP_001317366.1:p.Ser506Leu
  • NP_001361554.1:p.Ser501Leu
  • NP_002825.3:p.Ser502Leu
  • NP_002825.3:p.Ser502Leu
  • LRG_614t1:c.1505C>T
  • LRG_614:g.75350C>T
  • LRG_614p1:p.Ser502Leu
  • NC_000012.11:g.112926885C>T
  • NM_002834.3:c.1505C>T
  • NM_002834.4:c.1505C>T
  • NM_080601.1:c.*2448C>T
  • c.1505C>T
Protein change:
S501L
Links:
dbSNP: rs397507544
NCBI 1000 Genomes Browser:
rs397507544
Molecular consequence:
  • NM_001330437.2:c.1517C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.1502C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.1505C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000061281Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Jan 15, 2013) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided33not providednot providednot providedclinical testing

Citations

PubMed

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

PTPN11 gene analysis in 74 Brazilian patients with Noonan syndrome or Noonan-like phenotype.

Bertola DR, Pereira AC, Albano LM, De Oliveira PS, Kim CA, Krieger JE.

Genet Test. 2006 Fall;10(3):186-91.

PubMed [citation]
PMID:
17020470
See all PubMed Citations (8)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061281.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (8)

Description

The Ser502Leu variant has been reported in the literature in two individuals wit h clinical features of Noonan syndrome and/or LEOPARD syndrome (Tartaglia 2006, Ko 2008). Our laboratory has identified this variant in one proband where parent al testing was performed and showed the variant occurred de novo (LMM unpublishe d data). This variant has also been identified as a somatic variant in individua ls with hematologic malignancies including AML and ALL (Goemans 2005, Paulsson 2 007). In addition, three other amino acid changes at this location (Ser502Thr, Ser502Pro, Ser502Ala) have been associated with the clinical features of Noonan syndrome and have also been identified as somatic variants in individuals with h ematologic malignancies (Aoki 2008). The Ser502 residue is conserved across spec ies and computational analyses (biochemical amino acid properties, AlignGVGD, Po lyPhen2, and SIFT) suggest that the Ser502Leu variant may impact the normal func tion of the protein. In summary, this variant meets our criteria to be classifie d as pathogenic (http://pcpgm.partners.org/LMM) based upon the de novo occurrenc e combined with available published literature.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided3not provided3not provided

Last Updated: Nov 24, 2024