NM_002834.5(PTPN11):c.181G>A (p.Asp61Asn) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 2017
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:: RCV000576434.3

Allele description [Variation Report for NM_002834.5(PTPN11):c.181G>A (p.Asp61Asn)]

NM_002834.5(PTPN11):c.181G>A (p.Asp61Asn)

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.181G>A (p.Asp61Asn)

Other names:

p.D61N:GAT>AAT

HGVS:

NC_000012.12:g.112450361G>A
NG_007459.1:g.36630G>A
NM_001330437.2:c.181G>A
NM_001374625.1:c.178G>A
NM_002834.5:c.181G>AMANE SELECT
NM_080601.3:c.181G>A
NP_001317366.1:p.Asp61Asn
NP_001361554.1:p.Asp60Asn
NP_002825.3:p.Asp61Asn
NP_542168.1:p.Asp61Asn
LRG_614t1:c.181G>A
LRG_614:g.36630G>A
NC_000012.11:g.112888165G>A
NM_001330437.1:c.181G>A
NM_002834.3:c.181G>A
NM_002834.4:c.181G>A
NM_080601.1:c.181G>A
Q06124:p.Asp61Asn

Protein change:

D60N

Links:

UniProtKB: Q06124#VAR_015604; dbSNP: rs397507510

NCBI 1000 Genomes Browser:

rs397507510

Molecular consequence:

NM_001330437.2:c.181G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.181G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.181G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Noonan syndrome 1 (NS1)
Synonyms:: Turner Syndrome, Male; Turner phenotype with normal karyotype; Female pseudo-Turner syndrome
Identifiers:: MONDO: MONDO:0008104; MedGen: C4551602; Orphanet: 648; OMIM: 163950

Name:: LEOPARD syndrome 1 (LPRD1)
Synonyms:: LENTIGINOSIS, CARDIOMYOPATHIC; MULTIPLE LENTIGINES SYNDROME
Identifiers:: MONDO: MONDO:0100082; MedGen: C4551484; Orphanet: 500; OMIM: 151100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000678232	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 1, 2017)	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

SCV000678232

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 1, 2017)

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	unknown	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 Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV000678232.1

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

Description

PTPN11 NM_002834.3 exon3 p.Asp61Asn (c.181G>A): This variant has been reported in the literature in at least 7 individuals with Noonan syndrome, including some individuals with juvenile myelomonocytic leukemia (JMML) (Tartaglia 2002 PMID:11992261, Strullu 2014 PMID:25097206, Joyce 2016 PMID:26242988, Van Trier 2016 PMID:27521173). This variant is not present in large control databases. This variant is present in ClinVar (Variation ID:40495). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Of note, this variant occurs within the N-SH2/PTP interaction domain, a critical region for the function of this gene, and increases the likelihood that this variant is damaging (Tartaglia 2002 PMID: 11992261. Strullu 2014 PMID:25097206). Several variants at this codon (p.Asp61Gly, p.Asp61Ala, p.Asp61His) have been reported in association with Noonan syndrome and as a de novo, suggesting that this codon may be particularly important. In summary, this variant is classified as pathogenic based on the data above (number of probands, absence from controls, presence in functionally critical region).

#	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: Mar 10, 2024

ClinVar

Relating variation to medicine