NM_002834.5(PTPN11):c.1403C>T (p.Thr468Met) AND PTPN11-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 18, 2024
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000723326.10

Allele description [Variation Report for NM_002834.5(PTPN11):c.1403C>T (p.Thr468Met)]

NM_002834.5(PTPN11):c.1403C>T (p.Thr468Met)

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.1403C>T (p.Thr468Met)

Other names:

p.T468M:ACG>ATG; NM_002834.4(PTPN11):c.1403C>T

HGVS:

NC_000012.12:g.112488466C>T
NG_007459.1:g.74735C>T
NM_001330437.2:c.1415C>T
NM_001374625.1:c.1400C>T
NM_002834.5:c.1403C>TMANE SELECT
NP_001317366.1:p.Thr472Met
NP_001317366.1:p.Thr472Met
NP_001361554.1:p.Thr467Met
NP_002825.3:p.Thr468Met
NP_002825.3:p.Thr468Met
LRG_614t1:c.1403C>T
LRG_614:g.74735C>T
LRG_614p1:p.Thr468Met
NC_000012.11:g.112926270C>T
NM_001330437.1:c.1415C>T
NM_002834.3:c.1403C>T
NM_002834.4:c.1403C>T
c.1403C>T

Protein change:

T467M; THR468MET

Links:

OMIM: 176876.0006; dbSNP: rs121918457

NCBI 1000 Genomes Browser:

rs121918457

Molecular consequence:

NM_001330437.2:c.1415C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.1400C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.1403C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: PTPN11-related disorder
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000854720	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Pathogenic (Jul 5, 2018)	germline	clinical testing
SCV005360773	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Pathogenic (Jul 18, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000854720

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

no assertion criteria provided

Pathogenic
(Jul 5, 2018)

germline

clinical testing

SCV005360773

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Pathogenic
(Jul 18, 2024)

germline

clinical testing

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV000854720.1

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

#	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

From PreventionGenetics, part of Exact Sciences, SCV005360773.1

#	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.1403C>T variant is predicted to result in the amino acid substitution p.Thr468Met. This variant has been well documented as pathogenic in multiple unrelated individuals with Noonan syndrome with or without multiple lentigines (see for example - Digilio et al. 2002. PubMed ID: 12058348; Alfieri et al. 2011. PubMed ID: 21910245). At PreventionGenetics, we previously identified this variant in several other affected patients. Functional studies find this variant results in decreased protein tyrosine phosphatase activity inhibiting EGF-evoked Erk activation (Hanna et al. 2006. PubMed ID: 16638574; Kontaridis et al. 2006. PubMed ID: 16377799). This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD. This variant is interpreted as pathogenic.

#	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: Oct 13, 2024

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