NM_002834.5(PTPN11):c.184T>C (p.Tyr62His) AND Noonan syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 30, 2024
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:: RCV004698371.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.184T>C (p.Tyr62His)]

NM_002834.5(PTPN11):c.184T>C (p.Tyr62His)

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.184T>C (p.Tyr62His)

HGVS:

NC_000012.12:g.112450364T>C
NG_007459.1:g.36633T>C
NM_001330437.2:c.184T>C
NM_001374625.1:c.181T>C
NM_002834.5:c.184T>CMANE SELECT
NM_080601.3:c.184T>C
NP_001317366.1:p.Tyr62His
NP_001361554.1:p.Tyr61His
NP_002825.3:p.Tyr62His
NP_002825.3:p.Tyr62His
NP_542168.1:p.Tyr62His
LRG_614t1:c.184T>C
LRG_614:g.36633T>C
LRG_614p1:p.Tyr62His
NC_000012.11:g.112888168T>C
NM_002834.3:c.184T>C

Protein change:

Y61H

Molecular consequence:

NM_001330437.2:c.184T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.181T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.184T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.184T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Noonan syndrome (NS)
Synonyms:: Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:: MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005199862	Laboratory of Otorhinolaryngology, Head and Neck Surgery, Inje University Ilsan Paik Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 30, 2024)	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

SCV005199862

Laboratory of Otorhinolaryngology, Head and Neck Surgery, Inje University Ilsan Paik Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 30, 2024)

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	yes	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 Laboratory of Otorhinolaryngology, Head and Neck Surgery, Inje University Ilsan Paik Hospital, SCV005199862.1

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

Description

The c.184T>C variant is a missense variant in PTPN11 and has not been reported with suspected or confirmed Noonan syndrome in a population databases (gnomAD no frequency). This variant has been identified by our laboratory in one individual with clinical features of Noonan Syndrome and was absent from large population studies. This gain-of-function variant is expected to result in an disrupted protein product, and classified as likely pathogenic for Noonan syndrome based on the ACMG/AMP criteria.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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