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

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 16, 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:
RCV002408496.2

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:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002711072Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 16, 2019) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (12)

Details of each submission

From Ambry Genetics, SCV002711072.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

The p.D61N pathogenic mutation (also known as c.181G>A), located in coding exon 3 of the PTPN11 gene, results from a G to A substitution at nucleotide position 181. The aspartic acid at codon 61 is replaced by asparagine, an amino acid with highly similar properties. This pathogenic variant has been reported in multiple individuals with confirmed or suspected Noonan syndrome, including multiple de novo cases (Tartaglia M et al. Am. J. Hum. Genet., 2002 Jun;70:1555-63; Ferreira LV et al. J. Clin. Endocrinol. Metab., 2005 Sep;90:5156-60; Ferrero GB et al. Eur J Med Genet Jul;51:566-72; Derbent M et al. Am. J. Med. Genet. A, 2010 Nov;152A:2768-74; Lee BH et al. J. Pediatr., 2011 Dec;159:1029-35; Pasmant E et al. Am. J. Med. Genet. A, 2012 Sep;158A:2290-1; Strullu M et al. J. Med. Genet., 2014 Oct;51:689-97; van Trier DC et al. Int. J. Pediatr. Otorhinolaryngol., 2015 Jun;79:874-8; Atik T et al. Indian J Pediatr, 2016 Jun;83:517-21; Joyce S et al. Eur. J. Hum. Genet., 2016 May;24:690-6). This variant is located in the NSH2 domain, which interacts with the PTP domain to regulate switching of the resulting protein between its inactive and active conformations (Tartaglia M et al. Nat. Genet., 2001 Dec;29:465-8; Tartaglia M et al. Am. J. Hum. Genet., 2006 Feb;78:279-90) and other disease-causing variants at the same codon (p.D61G, p.D61H, p.D61A) have been described (Strullu M et al. J. Med. Genet., 2014 Oct;51:689-97; Tartaglia M et al. Am. J. Hum. Genet., 2002 Jun;70:1555-63). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024