NM_002834.5(PTPN11):c.155C>T (p.Thr52Ile) AND RASopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 15, 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:: RCV000809051.5

Allele description [Variation Report for NM_002834.5(PTPN11):c.155C>T (p.Thr52Ile)]

NM_002834.5(PTPN11):c.155C>T (p.Thr52Ile)

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.155C>T (p.Thr52Ile)

Other names:

p.T52I:ACC>ATC; NM_002834.4(PTPN11):c.155C>T

HGVS:

NC_000012.12:g.112450335C>T
NG_007459.1:g.36604C>T
NM_001330437.2:c.155C>T
NM_001374625.1:c.152C>T
NM_002834.5:c.155C>TMANE SELECT
NM_080601.3:c.155C>T
NP_001317366.1:p.Thr52Ile
NP_001361554.1:p.Thr51Ile
NP_002825.3:p.Thr52Ile
NP_542168.1:p.Thr52Ile
LRG_614t1:c.155C>T
LRG_614:g.36604C>T
NC_000012.11:g.112888139C>T
NM_002834.3:c.155C>T
NM_002834.4:c.155C>T
NM_080601.1:c.155C>T
c.155C>T

Protein change:

T51I

Links:

dbSNP: rs397507503

NCBI 1000 Genomes Browser:

rs397507503

Molecular consequence:

NM_001330437.2:c.155C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374625.1:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002834.5:c.155C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080601.3:c.155C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

Recent activity

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Homo sapiens calpain 1, (mu/I) large subunit (CAPN1), mRNA
Homo sapiens calpain 1, (mu/I) large subunit (CAPN1), mRNA
gi|11386176|ref|NM_005186.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000949188	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 15, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22465605, 25804457, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000949188

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 15, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Citations

PubMed

Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy.

Ezquieta B, Santomé JL, Carcavilla A, Guillén-Navarro E, Pérez-Aytés A, Sánchez del Pozo J, García-Miñaur S, Castillo E, Alonso M, Vendrell T, Santana A, Maroto E, Galbis L.

Rev Esp Cardiol (Engl Ed). 2012 May;65(5):447-55. doi: 10.1016/j.recesp.2011.12.016. Epub 2012 Mar 31. English, Spanish.

PubMed [citation]

PMID:: 22465605

Novel mutations in PTPN11 gene in two girls with Noonan syndrome phenotype.

Gulec EY, Ocak Z, Candan S, Ataman E, Yarar C.

Int J Cardiol. 2015;186:13-5. doi: 10.1016/j.ijcard.2015.03.260. Epub 2015 Mar 19. No abstract available.

PubMed [citation]

PMID:: 25804457

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000949188.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

ClinVar contains an entry for this variant (Variation ID: 40484). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt PTPN11 function. This missense change has been observed in individuals with clinical features of Noonan syndrome (PMID: 22465605, 25804457; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 52 of the PTPN11 protein (p.Thr52Ile).

#	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: Sep 29, 2024

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