NM_000314.8(PTEN):c.182A>G (p.His61Arg) AND PTEN hamartoma tumor syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Aug 31, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000490582.3

Allele description [Variation Report for NM_000314.8(PTEN):c.182A>G (p.His61Arg)]

NM_000314.8(PTEN):c.182A>G (p.His61Arg)

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.182A>G (p.His61Arg)
HGVS:
  • NC_000010.11:g.87925530A>G
  • NG_007466.2:g.67092A>G
  • NM_000314.8:c.182A>GMANE SELECT
  • NM_001304717.5:c.701A>G
  • NM_001304718.2:c.-541-5516A>G
  • NP_000305.3:p.His61Arg
  • NP_001291646.4:p.His234Arg
  • LRG_311t1:c.182A>G
  • LRG_311:g.67092A>G
  • NC_000010.10:g.89685287A>G
  • NM_000314.4:c.182A>G
  • NM_000314.6:c.182A>G
  • P60484:p.His61Arg
Protein change:
H234R
Links:
UniProtKB: P60484#VAR_026253; dbSNP: rs398123316
NCBI 1000 Genomes Browser:
rs398123316
Molecular consequence:
  • NM_001304718.2:c.-541-5516A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000314.8:c.182A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001304717.5:c.701A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000579264Herman Laboratory,Nationwide Children's Hospitalcriteria provided, single submitter
Pathogenic
(Mar 1, 2017)
paternalclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001499509Invitaecriteria provided, single submitter
Uncertain significance
(Aug 31, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Caucasianpaternalyes1not providednot provided1yesclinical testing

Citations

PubMed

A retrospective chart review of the features of PTEN hamartoma tumour syndrome in children.

Hansen-Kiss E, Beinkampen S, Adler B, Frazier T, Prior T, Erdman S, Eng C, Herman G.

J Med Genet. 2017 Jul;54(7):471-478. doi: 10.1136/jmedgenet-2016-104484. Epub 2017 May 19.

PubMed [citation]
PMID:
28526761

A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands.

Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C.

Am J Hum Genet. 2011 Jan 7;88(1):42-56. doi: 10.1016/j.ajhg.2010.11.013. Epub 2010 Dec 30.

PubMed [citation]
PMID:
21194675
PMCID:
PMC3014373
See all PubMed Citations (6)

Details of each submission

From Herman Laboratory,Nationwide Children's Hospital, SCV000579264.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Caucasian1not providedyesclinical testing PubMed (1)

Description

Macrocephaly (+4.7 SD)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyes1Bloodnot provided1not providednot providednot provided

From Invitae, SCV001499509.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces histidine with arginine at codon 61 of the PTEN protein (p.His61Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome (PMID: 28526761, 21194675, 21659347, 20600018). ClinVar contains an entry for this variant (Variation ID: 189402). This variant has been reported to affect PTEN protein function (PMID: 10866302). 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: Nov 27, 2021

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