NM_002834.5(PTPN11):c.173_175del (p.Asn58del) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 10, 2023
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:: RCV003736524.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.173_175del (p.Asn58del)]

NM_002834.5(PTPN11):c.173_175del (p.Asn58del)

Gene:

PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q24.13

Genomic location:

Preferred name:

NM_002834.5(PTPN11):c.173_175del (p.Asn58del)

HGVS:

NC_000012.12:g.112450353_112450355del
NG_007459.1:g.36622_36624del
NM_001330437.2:c.173_175del
NM_001374625.1:c.170_172del
NM_002834.5:c.173_175delMANE SELECT
NM_080601.3:c.173_175del
NP_001317366.1:p.Asn58del
NP_001361554.1:p.Asn57del
NP_002825.3:p.Asn58del
NP_002825.3:p.Asn58del
NP_542168.1:p.Asn58del
LRG_614t1:c.173_175del
LRG_614:g.36622_36624del
LRG_614p1:p.Asn58del
NC_000012.11:g.112888157_112888159del
NM_002834.3:c.173_175delACA

Protein change:

N57del

Molecular consequence:

NM_001330437.2:c.173_175del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001374625.1:c.170_172del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_002834.5:c.173_175del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_080601.3:c.173_175del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Homo sapiens sulfotransferase family, cytosolic, 1C, member 4, mRNA (cDNA clone ...
Homo sapiens sulfotransferase family, cytosolic, 1C, member 4, mRNA (cDNA clone MGC:149521 IMAGE:40115974), complete cds
gi|115527985|gb|BC125043.1|

Nucleotide
RecName: Full=Olfactory receptor 8H2; AltName: Full=Olfactory receptor OR11-171
RecName: Full=Olfactory receptor 8H2; AltName: Full=Olfactory receptor OR11-171
gi|38372643|sp|Q8N162.1|OR8H2_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004562405	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Likely pathogenic (Aug 10, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004562405

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Likely pathogenic
(Aug 10, 2023)

germline

clinical testing

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004562405.1

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

Description

The PTPN11 c.173_175del; p.Asn58del variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant deletes a critical residue that is directly involved in the interdomain interactions between the N-SH2 and PTPN domains (Tartaglia 2005). Additionally, other amino acid substitutions at this codon (His, Asp, Lys, Ser, Tyr) have been reported in individuals with Noonan syndrome and are considered pathogenic (Hakami 2016, Leach 2019). This variant deletes a single asparagine residue leaving the rest of the protein in-frame. Based on available information, this variant is considered to be likely pathogenic. References: Hakami F et al. Retrospective study of prenatal ultrasound findings in newborns with a Noonan spectrum disorder. Prenat Diagn. 2016 May;36(5):418-23. PMID: 26918529. Leach NT et al. Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions. Genet Med. 2019 Feb;21(2):417-425. PMID: 29907801. Tartaglia M et al. Germ-line and somatic PTPN11 mutations in human disease. Eur J Med Genet. 2005 Apr-Jun;48(2):81-96. PMID: 16053901.

#	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: Feb 28, 2024

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