NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jul 13, 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:: RCV000254683.7

Allele description [Variation Report for NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp)]

NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp)

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.228G>T (p.Glu76Asp)

Other names:

p.E76D:GAG>GAT

HGVS:

NC_000012.12:g.112450408G>T
NG_007459.1:g.36677G>T
NM_001330437.2:c.228G>T
NM_001374625.1:c.225G>T
NM_002834.5:c.228G>TMANE SELECT
NM_080601.3:c.228G>T
NP_001317366.1:p.Glu76Asp
NP_001361554.1:p.Glu75Asp
NP_002825.3:p.Glu76Asp
NP_002825.3:p.Glu76Asp
NP_542168.1:p.Glu76Asp
LRG_614t1:c.228G>T
LRG_614:g.36677G>T
NC_000012.11:g.112888212G>T
NM_001330437.1:c.228G>T
NM_002834.3:c.228G>T
NM_002834.4:c.228G>T
Q06124:p.Glu76Asp
c.228G>T
p.(Glu76Asp)

Protein change:

E75D

Links:

UniProtKB: Q06124#VAR_015610; dbSNP: rs397507514

NCBI 1000 Genomes Browser:

rs397507514

Molecular consequence:

NM_001330437.2:c.228G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.225G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.228G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.228G>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000057383	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 25, 2022)	germline	clinical testing	Citation Link,
SCV000928217	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Pathogenic (Feb 11, 2019)	germline	clinical testing	Citation Link,
SCV005197297	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000057383

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 25, 2022)

germline

clinical testing

Citation Link,

SCV000928217

Blueprint Genetics

criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)

Pathogenic
(Feb 11, 2019)

germline

clinical testing

Citation Link,

SCV005197297

Clinical Genetics Laboratory, Skane University Hospital Lund

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 13, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000057383.15

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

Description

Reported previously in association with Noonan syndrome (Tartaglia et al., 2006; Musante et al., 2003); Published functional studies demonstrate a damaging effect; p.(E76D) results in abnormally increased activity levels of the PTPN11 protein (Tartaglia et al., 2006; Bocchinfuso et al., 2007); Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12634870, 20308328, 17177198, 29907801, 30029678, 16830086, 30050098, 32676024, 16358218, 24077912, 27535533, 11992261, 9491886, 16053901, 29493581)

#	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 Blueprint Genetics, SCV000928217.1

#	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 Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005197297.1

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

#	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

Last Updated: Oct 13, 2024

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