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NM_002834.5(PTPN11):c.661del (p.Arg220_Ile221insTer) AND Metachondromatosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 7, 2011
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:
RCV000037654.2

Allele description

NM_002834.5(PTPN11):c.661del (p.Arg220_Ile221insTer)

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.661del (p.Arg220_Ile221insTer)
HGVS:
  • NC_000012.12:g.112455968del
  • NG_007459.1:g.42237del
  • NM_001330437.2:c.661del
  • NM_001374625.1:c.658del
  • NM_002834.5:c.661delMANE SELECT
  • NM_080601.3:c.661del
  • NP_001317366.1:p.Arg220_Ile221insTer
  • NP_001361554.1:p.Arg219_Ile220insTer
  • NP_002825.3:p.Arg220_Ile221insTer
  • NP_542168.1:p.Arg220_Ile221insTer
  • LRG_614t1:c.661del
  • LRG_614:g.42237del
  • NC_000012.11:g.112893772del
  • NC_000012.11:g.112893772delA
  • NM_002834.3:c.661delA
  • c.661delA
  • p.Ile221X
Links:
dbSNP: rs397516807
NCBI 1000 Genomes Browser:
rs397516807
Molecular consequence:
  • NM_001330437.2:c.661del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374625.1:c.658del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_002834.5:c.661del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_080601.3:c.661del - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Metachondromatosis (METCDS)
Identifiers:
MONDO: MONDO:0007979; MedGen: C0410530; Orphanet: 2499; OMIM: 156250

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000061316Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Sep 7, 2011) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical 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 Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000061316.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The Ile221X variant has not been reported in the literature nor previously ident ified in our laboratory in over 1,800 individuals tested. This variant leads to a premature stop codon at position 221, which is predicted to result in a trunca ted or absent protein. Nonsense variants and other loss-of-function variants hav e been identified as pathogenic in individuals with metachondromatosis (Sobreira 2010, Bowen 2011). Therefore, this variant is highly likely to be pathogenic. The presence of a heterozygous pathogenic loss-of-function variant in PTPN11 is consistent with a diagnosis of metachondromatosis but this information should be reconciled with the complete clinical history of this individual.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Apr 8, 2022