NM_000314.8(PTEN):c.331T>C (p.Trp111Arg) AND PTEN hamartoma tumor syndrome

Clinical significance:Likely pathogenic (Last evaluated: Nov 28, 2018)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000758231.3

Allele description [Variation Report for NM_000314.8(PTEN):c.331T>C (p.Trp111Arg)]

NM_000314.8(PTEN):c.331T>C (p.Trp111Arg)

Gene:
PTEN:phosphatase and tensin homolog [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.31
Genomic location:
Preferred name:
NM_000314.8(PTEN):c.331T>C (p.Trp111Arg)
Other names:
NM_000314.6(PTEN):c.331T>C
HGVS:
  • NC_000010.11:g.87933090T>C
  • NG_007466.2:g.74652T>C
  • NM_000314.8:c.331T>CMANE SELECT
  • NM_001304717.5:c.850T>C
  • NM_001304718.2:c.-420T>C
  • NP_000305.3:p.Trp111Arg
  • NP_001291646.4:p.Trp284Arg
  • LRG_311t1:c.331T>C
  • LRG_311:g.74652T>C
  • LRG_311p1:p.Trp111Arg
  • NC_000010.10:g.89692847T>C
  • NM_000314.4:c.331T>C
Protein change:
W111R
Links:
dbSNP: rs398123321
NCBI 1000 Genomes Browser:
rs398123321
Molecular consequence:
  • NM_001304718.2:c.-420T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000314.8:c.331T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304717.5:c.850T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
PTEN hamartoma tumor syndrome (PHTS)
Synonyms:
PTEN Hamartomatous Tumour Syndrome
Identifiers:
MONDO: MONDO:0017623; MedGen: C1959582

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000886868ClinGen PTEN Variant Curation Expert Panelreviewed by expert panel
Likely pathogenic
(Nov 28, 2018)
germlinecuration

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

Citation Link,

SCV001225621Invitaecriteria provided, single submitter
Uncertain significance
(Oct 28, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

Analysis of protein-coding genetic variation in 60,706 humans.

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, et al.

Nature. 2016 Aug 18;536(7616):285-91. doi: 10.1038/nature19057.

PubMed [citation]
PMID:
27535533
PMCID:
PMC5018207

Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes.

Zhou X, Hampel H, Thiele H, Gorlin RJ, Hennekam RC, Parisi M, Winter RM, Eng C.

Lancet. 2001 Jul 21;358(9277):210-1.

PubMed [citation]
PMID:
11476841
See all PubMed Citations (5)

Details of each submission

From ClinGen PTEN Variant Curation Expert Panel, SCV000886868.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (3)

Description

PTEN c.331T>C (p.W111R) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PS3: Phosphatase activity <50% of wild type (PMID 29785012, 29706350) PM2: Absent in large sequenced populations (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001225621.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces tryptophan with arginine at codon 111 of the PTEN protein (p.Trp111Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Proteus syndrome (PMID: 11476841). ClinVar contains an entry for this variant (Variation ID: 92820). This variant has been reported to affect PTEN protein function (PMID: 29706350, 29785012). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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