ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.701G>A (p.Arg234Gln) (rs121909235)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566397 SCV000665310 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Deficient protein function in appropriate functional assay(s),Insufficient evidence
ClinGen PTEN Variant Curation Expert Panel RCV000540379 SCV000930139 uncertain significance PTEN hamartoma tumor syndrome 2018-11-28 reviewed by expert panel curation PTEN c.701G>A (p.Arg234Gln) is currently classified as a variant of uncertain significance 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). 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.
Color RCV000566397 SCV000913519 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-19 criteria provided, single submitter clinical testing
Invitae RCV000540379 SCV000645613 uncertain significance PTEN hamartoma tumor syndrome 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 234 of the PTEN protein (p.Arg234Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (rs121909235, ExAC no frequency). This variant has been reported in an individual affected with glioma (PMID: 12085208) and an individual affected with pancreatic adenocarcinoma (PMID: 28755079). ClinVar contains an entry for this variant (Variation ID: 7840). Experimental studies in a glioma cell line have shown that this missense change results in increased cell proliferation, constitutive PKB/Akt activation, and an inability to induce apoptosis (PMID: 12085208). 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.
OMIM RCV000008288 SCV000028495 risk factor Glioma susceptibility 2 2002-05-20 no assertion criteria provided literature only
OMIM RCV000008289 SCV000028496 pathogenic Meningioma 2002-05-20 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.