ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.509G>T (p.Ser170Ile) (rs876660507)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217155 SCV000277993 pathogenic Hereditary cancer-predisposing syndrome 2018-10-10 criteria provided, single submitter clinical testing The p.S170I pathogenic mutation (also known as c.509G>T), located in coding exon 6 of the PTEN gene, results from a G to T substitution at nucleotide position 509. The serine at codon 170 is replaced by isoleucine, an amino acid with dissimilar properties. This mutation has been reported in multiple individuals meeting classic or relaxed diagnostic criteria for Cowden syndrome (<span style="background-color:initial">Tan MH et al. Am. J. Hum. Genet. 2011 Jan; 88(1):42-56; Ngeow J et al. J. Clin. Oncol. 2014 Jun; 32(17):1818-24; Nizialek EA et al. Eur. J. Hum. Genet. 2015 Nov;23(11):1538-43). Another mutation at the same position, p.S170R, has also been described in individuals meeting classic or relaxed criteria for Cowden syndrome (Tan MH et al. Am. J. Hum. Genet<span style="background-color:initial">. 2011 Jan; 88(1):42-56; <span style="background-color:initial">de Leon MP et al. Dig Liver Dis 2013 Jan; 45(1):75-8). <span style="background-color:initial">Based on the available evidence, <span style="background-color:initial">this alteration <span style="background-color:initial">is classified as a pathogenic mutation.
Invitae RCV001053859 SCV001218142 pathogenic PTEN hamartoma tumor syndrome 2019-08-24 criteria provided, single submitter clinical testing This sequence change replaces serine with isoleucine at codon 170 of the PTEN protein (p.Ser170Ile). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS), collectively also known as PTEN hamartoma tumor syndrome (PMID: 24778394, 21659347, Invitae). ClinVar contains an entry for this variant (Variation ID: 233590). This variant has been reported to affect PTEN protein function (PMID: 29706350). This variant disrupts the p.Ser170 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been observed in individuals with PTEN-related conditions (PMID: 21194675, 21659347, 10400993, 20712882, 23117110), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785382 SCV000923953 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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.