NM_002834.5(PTPN11):c.211T>C (p.Phe71Leu) AND Rasopathy

Clinical significance:Pathogenic (Last evaluated: Jun 11, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000686123.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.211T>C (p.Phe71Leu)]

NM_002834.5(PTPN11):c.211T>C (p.Phe71Leu)

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.211T>C (p.Phe71Leu)
Other names:
p.F71L:TTT>CTT
HGVS:
  • NC_000012.12:g.112450391T>C
  • NG_007459.1:g.36660T>C
  • NM_001330437.2:c.211T>C
  • NM_001374625.1:c.208T>C
  • NM_002834.5:c.211T>CMANE SELECT
  • NM_080601.3:c.211T>C
  • NP_001317366.1:p.Phe71Leu
  • NP_001361554.1:p.Phe70Leu
  • NP_002825.3:p.Phe71Leu
  • NP_542168.1:p.Phe71Leu
  • LRG_614t1:c.211T>C
  • LRG_614:g.36660T>C
  • NC_000012.11:g.112888195T>C
  • NM_002834.3:c.211T>C
  • Q06124:p.Phe71Leu
Protein change:
F70L
Links:
UniProtKB: Q06124#VAR_015995; dbSNP: rs397507512
NCBI 1000 Genomes Browser:
rs397507512
Molecular consequence:
  • NM_001330437.2:c.211T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.208T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.211T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.211T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Rasopathy
Synonyms:
rasopathies; Noonan spectrum disorder
Identifiers:
MONDO: MONDO:0021060; MedGen: CN166718

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000813626Invitaecriteria provided, single submitter
Pathogenic
(Jun 11, 2018)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis.

Loh ML, Vattikuti S, Schubbert S, Reynolds MG, Carlson E, Lieuw KH, Cheng JW, Lee CM, Stokoe D, Bonifas JM, Curtiss NP, Gotlib J, Meshinchi S, Le Beau MM, Emanuel PD, Shannon KM.

Blood. 2004 Mar 15;103(6):2325-31. Epub 2003 Nov 26.

PubMed [citation]
PMID:
14644997

PTPN11 analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings.

Lee KA, Williams B, Roza K, Ferguson H, David K, Eddleman K, Stone J, Edelmann L, Richard G, Gelb BD, Kornreich R.

Clin Genet. 2009 Feb;75(2):190-4. doi: 10.1111/j.1399-0004.2008.01085.x. Epub 2008 Aug 26.

PubMed [citation]
PMID:
18759865
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000813626.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces phenylalanine with leucine at codon 71 of the PTPN11 protein (p.Phe71Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Noonan syndrome (PMID: 12634870, 25097206, 18759865, 19737548, Invitae), including at least one de novo observation,  and in an individual affected with myelodysplastic syndrome (PMID: 14644997). In addition, a different variant (c.211T>G) giving rise to the same protein effect observed here (p.Phe71Leu) has been reported in an individual affected with Noonan syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 40499). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change is located in a region of the PTPN11 protein where a significant number of previously reported PTPN11 missense mutations are found (PMID: 18470943). These observations suggest that a missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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