NM_002834.5(PTPN11):c.265_269del (p.Lys89fs) AND RASopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 30, 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:: RCV002537612.3

Allele description [Variation Report for NM_002834.5(PTPN11):c.265_269del (p.Lys89fs)]

NM_002834.5(PTPN11):c.265_269del (p.Lys89fs)

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.265_269del (p.Lys89fs)

HGVS:

NC_000012.12:g.112450445_112450449del
NG_007459.1:g.36714_36718del
NM_001330437.2:c.265_269del
NM_001374625.1:c.262_266del
NM_002834.5:c.265_269delMANE SELECT
NM_080601.3:c.265_269del
NP_001317366.1:p.Lys89fs
NP_001361554.1:p.Lys88fs
NP_002825.3:p.Lys89fs
NP_542168.1:p.Lys89fs
LRG_614:g.36714_36718del
NC_000012.11:g.112888248_112888252del
NC_000012.11:g.112888249_112888253del
NM_002834.4:c.265_269delAAAGA

Protein change:

K88fs

Links:

Molecular consequence:

NM_001330437.2:c.265_269del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374625.1:c.262_266del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002834.5:c.265_269del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_080601.3:c.265_269del - 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
SCV002965161	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 30, 2023)	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

SCV002965161

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 30, 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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002965161.2

#	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.Lys89Glufs*7) in the PTPN11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTPN11 are known to be pathogenic (PMID: 20577567, 21533187). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. ClinVar contains an entry for this variant (Variation ID: 981580). For these reasons, this variant has been classified 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: Sep 29, 2024

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