NM_002834.5(PTPN11):c.409del (p.Val137fs) AND RASopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 13, 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:: RCV001235274.5

Allele description [Variation Report for NM_002834.5(PTPN11):c.409del (p.Val137fs)]

NM_002834.5(PTPN11):c.409del (p.Val137fs)

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.409del (p.Val137fs)

HGVS:

NC_000012.12:g.112453271del
NG_007459.1:g.39540del
NM_001330437.2:c.409del
NM_001374625.1:c.406del
NM_002834.5:c.409delMANE SELECT
NM_080601.3:c.409del
NP_001317366.1:p.Val137fs
NP_001361554.1:p.Val136fs
NP_002825.3:p.Val137fs
NP_542168.1:p.Val137fs
LRG_614t1:c.409del
LRG_614:g.39540del
NC_000012.11:g.112891075del
NM_002834.3:c.409del

Protein change:

V136fs

Links:

dbSNP: rs2038103354

NCBI 1000 Genomes Browser:

rs2038103354

Molecular consequence:

NM_001330437.2:c.409del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374625.1:c.406del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002834.5:c.409del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_080601.3:c.409del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001407953	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 13, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20577567, 21533187, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001407953

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 13, 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

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

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

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001407953.5

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

Description

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 not been reported in the literature in individuals with PTPN11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val137Tyrfs*31) in the PTPN11 gene. It is expected to result in an absent or disrupted protein product.

#	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 20, 2024

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