NM_002834.5(PTPN11):c.412C>T (p.Arg138Ter) AND RASopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 25, 2019
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:: RCV001205820.7

Allele description [Variation Report for NM_002834.5(PTPN11):c.412C>T (p.Arg138Ter)]

NM_002834.5(PTPN11):c.412C>T (p.Arg138Ter)

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.412C>T (p.Arg138Ter)

HGVS:

NC_000012.12:g.112453274C>T
NG_007459.1:g.39543C>T
NM_001330437.2:c.412C>T
NM_001374625.1:c.409C>T
NM_002834.5:c.412C>TMANE SELECT
NM_080601.3:c.412C>T
NP_001317366.1:p.Arg138Ter
NP_001361554.1:p.Arg137Ter
NP_002825.3:p.Arg138Ter
NP_542168.1:p.Arg138Ter
LRG_614t1:c.412C>T
LRG_614:g.39543C>T
NC_000012.11:g.112891078C>T
NM_002834.3:c.412C>T

Protein change:

R137*; ARG138TER

Links:

OMIM: 176876.0026; dbSNP: rs267606989

NCBI 1000 Genomes Browser:

rs267606989

Molecular consequence:

NM_001330437.2:c.412C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374625.1:c.409C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_002834.5:c.412C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_080601.3:c.412C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001377096	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 25, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21533187, 20577567, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001377096

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 25, 2019)

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

Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome.

Bowen ME, Boyden ED, Holm IA, Campos-Xavier B, Bonafé L, Superti-Furga A, Ikegawa S, Cormier-Daire V, Bovée JV, Pansuriya TC, de Sousa SB, Savarirayan R, Andreucci E, Vikkula M, Garavelli L, Pottinger C, Ogino T, Sakai A, Regazzoni BM, Wuyts W, Sangiorgi L, Pedrini E, et al.

PLoS Genet. 2011 Apr;7(4):e1002050. doi: 10.1371/journal.pgen.1002050. Epub 2011 Apr 14.

PubMed [citation]

PMID:: 21533187
PMCID:: PMC3077396

Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene.

Sobreira NL, Cirulli ET, Avramopoulos D, Wohler E, Oswald GL, Stevens EL, Ge D, Shianna KV, Smith JP, Maia JM, Gumbs CE, Pevsner J, Thomas G, Valle D, Hoover-Fong JE, Goldstein DB.

PLoS Genet. 2010 Jun 17;6(6):e1000991. doi: 10.1371/journal.pgen.1000991.

PubMed [citation]

PMID:: 20577567
PMCID:: PMC2887469

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001377096.5

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

Description

This sequence change creates a premature translational stop signal (p.Arg138*) in the PTPN11 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PTPN11 are known to be pathogenic (PMID: 20577567, 21533187). This variant has been observed to segregate with metachondromatosis in a family (PMID: 20577567). ClinVar contains an entry for this variant (Variation ID: 13348). This variant is not present in population databases (ExAC no frequency).

#	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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