NM_000314.4(PTEN):c.104T>G (p.Met35Arg) AND Cowden syndrome

Clinical significance:Pathogenic (Last evaluated: Mar 1, 2013)

Review status:(1/4)1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000008271.1

Allele description [Variation Report for NM_000314.4(PTEN):c.104T>G (p.Met35Arg)]

Gene:
PTEN:phosphatase and tensin homolog [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.31
Genomic location:
Preferred name:
NM_000314.4(PTEN):c.104T>G (p.Met35Arg)
HGVS:
  • NC_000010.11:g.87894049T>G
  • NG_007466.2:g.35611T>G
  • NM_000314.4:c.104T>G
  • NP_000305.3:p.Met35Arg
  • LRG_311t1:c.104T>G
  • LRG_311:g.35611T>G
  • LRG_311p1:p.Met35Arg
  • NC_000010.10:g.89653806T>G
Protein change:
M35R; MET35ARG
Links:
OMIM: 601728.0011; dbSNP: 121909225
NCBI 1000 Genomes Browser:
rs121909225
Molecular consequence:
  • NM_000314.4:c.104T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cowden syndrome (CD)
Synonyms:
Lhermitte-Duclos Disease; COWDEN DISEASE 1; COWDEN SYNDROME 1; See all synonyms [MedGen]
Identifiers:
MedGen: C0018553; OMIM: 158350
Prevalence:
1 in 200,000 http://www.ncbi.nlm.nih.gov/books/NBK1488/

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000028478OMIMPathogenic
(Mar 1, 2013)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

PTEN germ-line mutations in juvenile polyposis coli.

Olschwang S, Serova-Sinilnikova OM, Lenoir GM, Thomas G.

Nat Genet. 1998 Jan;18(1):12-4. No abstract available.

PubMed [citation]
PMID:
9425889

PTEN and inherited hamartoma-cancer syndromes.

Eng C, Peacocke M.

Nat Genet. 1998 Jul;19(3):223. No abstract available.

PubMed [citation]
PMID:
9662392
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000028478.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)

Description

In a patient considered to have juvenile polyposis coli, Olschwang et al. (1998) identified a T-to-G transversion in exon 2 predicted to substitute an arginine for the methionine at codon 35. The PTEN protein demonstrates exceedingly high phylogenic conservation, with the human protein identical to that of dog and differing from that of mouse by a single amino acid change at codon 398. Codon 35 occurs in the region of PTEN that presents significant homology with tensin (600076) and auxilin. Taken together, these observations suggested that the DNA variation in this patient was deleterious. The patient underwent gastroscopy and colonoscopy at 7 years of age, after a 3-year history of intermittent rectal bleeding. Juvenile polyps were found throughout the stomach, duodenum, and colon. At the age of 10 years, clinical evaluations had not revealed any extra-digestive manifestations that could be associated with Cowden disease. Both parents underwent colonoscopy that showed normal digestive tracts. The genotypes at 8 highly polymorphic microsatellite loci in the parents and patient confirmed mendelian inheritance. Sequencing of exon 2 amplified from the DNAs of both parents revealed only codon 35 for methionine, demonstrating that codon 35 of arginine was a new mutation.

Eng and Peacocke (1998) pointed out that the penetrance of Cowden syndrome (158350) is well under 10% below 15 years of age (Nelen et al., 1996); thus children with JPS, according to diagnostic criteria, may develop other features of Cowden syndrome as they age. Waite and Eng (2002) supported this conclusion and stated that juvenile intestinal polyposis is not a so-called PTEN hamartoma-tumor syndrome (PHTS). They suggested that the discovery of the germline PTEN mutation in an individual considered to have JPS should raise a suspicion that the clinical diagnosis is incorrect and that such an individual should be managed medically in the same manner as all patients with PHTS.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 21, 2014

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