NM_002834.5(PTPN11):c.166A>G (p.Ile56Val) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Aug 17, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000518841.3

Allele description [Variation Report for NM_002834.5(PTPN11):c.166A>G (p.Ile56Val)]

NM_002834.5(PTPN11):c.166A>G (p.Ile56Val)

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.166A>G (p.Ile56Val)
Other names:
p.I56V:ATT>GTT; NM_002834.4(PTPN11):c.166A>G
HGVS:
  • NC_000012.12:g.112450346A>G
  • NG_007459.1:g.36615A>G
  • NM_001330437.2:c.166A>G
  • NM_001374625.1:c.163A>G
  • NM_002834.4:c.166A>G
  • NM_002834.5:c.166A>GMANE SELECT
  • NM_080601.3:c.166A>G
  • NP_001317366.1:p.Ile56Val
  • NP_001361554.1:p.Ile55Val
  • NP_002825.3:p.Ile56Val
  • NP_002825.3:p.Ile56Val
  • NP_542168.1:p.Ile56Val
  • LRG_614t1:c.166A>G
  • LRG_614:g.36615A>G
  • NC_000012.11:g.112888150A>G
  • NM_002834.3:c.166A>G
Protein change:
I55V
Links:
dbSNP: rs397507504
NCBI 1000 Genomes Browser:
rs397507504
Molecular consequence:
  • NM_001330437.2:c.166A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.163A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.4:c.166A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.166A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.166A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000057358GeneDxcriteria provided, single submitter
Likely pathogenic
(Jul 26, 2017)
germlineclinical testing

Citation Link,

SCV000927861Blueprint Geneticscriteria provided, single submitter
Likely pathogenic
(Aug 17, 2018)
germlineclinical testing

Citation Link

Description

Patient analyzed with Noonan Syndrome Panel

SCV000927861

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000057358.14

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The I56V missense substitution has been observed previously in a patient with suspected Noonan syndrome (Atik et al., 2016). The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). I56V is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position within the SH2 domain that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (T52I, N58H/D/K, T59A, G60C/S/A, D61H/N/G/A) have been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

From Blueprint Genetics, SCV000927861.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 16, 2021

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