NM_002834.5(PTPN11):c.1052G>A (p.Arg351Gln) AND not specified

Germline classification:: Benign (1 submission)
Last evaluated:: Aug 9, 2021
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:: RCV001582506.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.1052G>A (p.Arg351Gln)]

NM_002834.5(PTPN11):c.1052G>A (p.Arg351Gln)

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.1052G>A (p.Arg351Gln)

Other names:

NM_002834.4(PTPN11):c.1052G>A

HGVS:

NC_000012.12:g.112477975G>A
NG_007459.1:g.64244G>A
NM_001330437.2:c.1052G>A
NM_001374625.1:c.1049G>A
NM_002834.5:c.1052G>AMANE SELECT
NM_080601.3:c.1052G>A
NP_001317366.1:p.Arg351Gln
NP_001361554.1:p.Arg350Gln
NP_002825.3:p.Arg351Gln
NP_002825.3:p.Arg351Gln
NP_542168.1:p.Arg351Gln
LRG_614t1:c.1052G>A
LRG_614:g.64244G>A
NC_000012.11:g.112915779G>A
NM_002834.3:c.1052G>A
NM_002834.4:c.1052G>A

Protein change:

R350Q

Links:

dbSNP: rs397507534

NCBI 1000 Genomes Browser:

rs397507534

Molecular consequence:

NM_001330437.2:c.1052G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.1049G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.1052G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.1052G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001821485	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Aug 9, 2021)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 15385933, 14644997, 19047918, 19179468, 17972951, 15710330, 25395418, 27069254 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001821485

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Aug 9, 2021)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group.

Loh ML, Reynolds MG, Vattikuti S, Gerbing RB, Alonzo TA, Carlson E, Cheng JW, Lee CM, Lange BJ, Meshinchi S; Children's Cancer Group..

Leukemia. 2004 Nov;18(11):1831-4.

PubMed [citation]

PMID:: 15385933

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

See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001821485.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Variant summary: PTPN11 c.1052G>A (p.Arg351Gln) results in a conservative amino acid change located in the PTP type protein phosphatase domain (IPR000242) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00043 in 251446 control chromosomes. The observed variant frequency is approximately 6.81 fold of the estimated maximal expected allele frequency for a pathogenic variant in PTPN11 causing Noonan Syndrome phenotype (6.3e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1052G>A in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories and an expert panel (ClinGen RASopathy Variant Curation Expert Panel) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign/likely benign, n=2; VUS, n=1). Based on the evidence outlined above, the variant was classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

ClinVar

Relating variation to medicine