NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp) AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Feb 21, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000153794.28

Allele description [Variation Report for NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)]

NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)

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.184T>G (p.Tyr62Asp)

Other names:

p.Y62D:TAC>GAC

HGVS:

NC_000012.12:g.112450364T>G
NG_007459.1:g.36633T>G
NM_001330437.2:c.184T>G
NM_001374625.1:c.181T>G
NM_002834.5:c.184T>GMANE SELECT
NM_080601.3:c.184T>G
NP_001317366.1:p.Tyr62Asp
NP_001317366.1:p.Tyr62Asp
NP_001361554.1:p.Tyr61Asp
NP_002825.3:p.Tyr62Asp
NP_002825.3:p.Tyr62Asp
NP_542168.1:p.Tyr62Asp
LRG_614t1:c.184T>G
LRG_614:g.36633T>G
LRG_614p1:p.Tyr62Asp
NC_000012.11:g.112888168T>G
NM_001330437.1:c.184T>G
NM_002834.3:c.184T>G
NM_002834.4(PTPN11):c.184T>G
NM_002834.4:c.184T>G
Q06124:p.Tyr62Asp

Protein change:

Y61D; TYR62ASP

Links:

UniProtKB: Q06124#VAR_015605; OMIM: 176876.0009; dbSNP: rs121918460

NCBI 1000 Genomes Browser:

rs121918460

Molecular consequence:

NM_001330437.2:c.184T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.181T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.184T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.184T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000057371	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 3, 2021)	germline	clinical testing	Citation Link,
SCV000203372	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Pathogenic (Feb 13, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11992261, 12325025, 12717436, 22711529 Citation Link,
SCV000207651	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	no assertion criteria provided	Pathogenic (Jan 15, 2015)	germline	clinical testing
SCV000265849	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 5, 2015)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22711529, 11992261, 16358218, 25741868
SCV000927995	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Pathogenic (Oct 16, 2018)	germline	clinical testing	Citation Link,
SCV001714421	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 21, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22711529, 12325025, 11992261, 31560489, 32164556, 25741868

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	8	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

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 (8)

Details of each submission

From GeneDx, SCV000057371.14

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate a profound effect on protein structure leading to re-arrangement and upregulation of its function, specifically by destabilizing the autoinhibited conformation of the SHP2 protein (Martinelli et al., 2012); The majority of missense variants in this gene are considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19077116, 28607217, 25337068, 19020799, 32164556, 24033266, 16358218, 15928039, 19352411, 17020470, 12717436, 12325025, 11992261, 24803665, 25533962, 22711529, 26817465, 29555671, 29670795, 28135719, 15240615, 28191890, 28991257, 30417923, 30050098, 29907801, 31219622, 31560489, 33300679, 32901917, 32368696, 31785789)

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

From Eurofins Ntd Llc (ga), SCV000203372.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

#	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		2	not provided	not provided	not provided

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV000207651.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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

From Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV000265849.1

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

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

From Blueprint Genetics, SCV000927995.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714421.2

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

Description

PS4, PS3, PM6

#	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		6	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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