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NM_002834.5(PTPN11):c.923A>C (p.Asn308Thr) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 13, 2015
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:
RCV002371807.2

Allele description [Variation Report for NM_002834.5(PTPN11):c.923A>C (p.Asn308Thr)]

NM_002834.5(PTPN11):c.923A>C (p.Asn308Thr)

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.923A>C (p.Asn308Thr)
Other names:
p.N308T:AAT>ACT
HGVS:
  • NC_000012.12:g.112477720A>C
  • NG_007459.1:g.63989A>C
  • NM_001330437.2:c.923A>C
  • NM_001374625.1:c.920A>C
  • NM_002834.5:c.923A>CMANE SELECT
  • NM_080601.3:c.923A>C
  • NP_001317366.1:p.Asn308Thr
  • NP_001361554.1:p.Asn307Thr
  • NP_002825.3:p.Asn308Thr
  • NP_542168.1:p.Asn308Thr
  • LRG_614t1:c.923A>C
  • LRG_614:g.63989A>C
  • NC_000012.11:g.112915524A>C
  • NM_002834.3:c.923A>C
  • NM_002834.4:c.923A>C
  • NM_080601.1:c.923A>C
  • c.923A>C
Protein change:
N307T
Links:
dbSNP: rs121918455
NCBI 1000 Genomes Browser:
rs121918455
Molecular consequence:
  • NM_001330437.2:c.923A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.920A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.923A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.923A>C - 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
SCV002687610Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 13, 2015) 		germlineclinical testing

PubMed (3)
[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

Genotype-phenotype correlations in Noonan syndrome.

Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, Tietze HU, Doerr HG, Hofbeck M, Singer H, Reis A, Rauch A.

J Pediatr. 2004 Mar;144(3):368-74.

PubMed [citation]
PMID:
15001945

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 (3)

Details of each submission

From Ambry Genetics, SCV002687610.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.N308T pathogenic mutation (also known as c.923A>C), located in coding exon 8 of the PTPN11 gene, results from an A to C substitution at nucleotide position 923. The asparagine at codon 308 is replaced by threonine, an amino acid with similar properties. In one study, this mutation was detected in an individual with a clinical diagnosis of Noonan syndrome (Pierpont EI, et al. Genes Brain Behav. 2009;8(3):275-82). This mutation was also described in two individuals who likely had clinical diagnoses of either Noonan syndrome or Leigus syndrome; however, clinical diagnoses were not confirmed (Tartaglia M et al. Am J Hum Genet. 2006; 78(2):279-290). The Asn308 residue has been presented as a mutational hot spot, and two different mutations located in this same residue, p.N308S and p.N308D, have been described in multiple individuals with Noonan syndrome (Qiu W, et al. BMC Struct. Biol. 2014;14():10); Tartaglia M, et al. Nat. Genet. 2001;29(4):465-8; Zenker M, et al. J. Pediatr. 2004;144(3):368-74). Based on the supporting evidence, p.N308T 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