NM_002834.5(PTPN11):c.228G>C (p.Glu76Asp) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 11, 2019
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:: RCV002453282.2

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

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

Other names:

p.E76D:GAG>GAC

HGVS:

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

Protein change:

E75D

Links:

UniProtKB: Q06124#VAR_015610; dbSNP: rs397507514

NCBI 1000 Genomes Browser:

rs397507514

Molecular consequence:

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

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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
SCV002738080	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 11, 2019)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 11704759, 11992261, 12634870, 15985475, 15987685, 16358218, 16830086, 18678287 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002738080

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 11, 2019)

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

Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome.

Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD.

Nat Genet. 2001 Dec;29(4):465-8. Erratum in: Nat Genet 2001 Dec;29(4):491. Nat Genet 2002 Jan;30(1):123.

PubMed [citation]

PMID:: 11704759

PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.

Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD.

Am J Hum Genet. 2002 Jun;70(6):1555-63. Epub 2002 May 1.

PubMed [citation]

PMID:: 11992261
PMCID:: PMC379142

See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV002738080.2

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

Description

The p.E76D pathogenic mutation (also known as c.228G>C), located in coding exon 3 of the PTPN11 gene, results from a G to C substitution at nucleotide position 228. The glutamic acid at codon 76 is replaced by aspartic acid, an amino acid with highly similar properties. This mutation has been reported in multiple individuals with Noonan syndrome (Tartaglia M et al. Am. J. Hum. Genet., 2006 Feb;78:279-90; Ferrero GB et al. Eur J Med Genet Jul;51:566-72). An alternate nucleotide change, c.228G>T, resulting in the same amino acid substitution p.E76D, has also been detected in Noonan syndrome cohorts (Musante L et al. Eur. J. Hum. Genet., 2003 Feb;11:201-6; Binder G et al. J. Clin. Endocrinol. Metab., 2005 Sep;90:5377-81; Tartaglia M et al. Am. J. Hum. Genet., 2006 Feb;78:279-90). Functional studies have shown that p.E76D leads to increased phosphatase activity (Tartaglia M et al. Am. J. Hum. Genet., 2006 Feb;78:279-90; Keilhack H et al. J. Biol. Chem., 2005 Sep;280:30984-93). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine