ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.634+2T>G

dbSNP: rs727504114
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
Eurofins Ntd Llc (ga) RCV000153791 SCV000203369 pathogenic not provided 2014-01-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491022 SCV000579987 pathogenic Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing The c.634+2T>G intronic pathogenic mutation results from a T to G substitution two nucleotides after coding exon 6 of the PTEN gene. This mutation was identified in a single individual meeting clinical diagnosis of Cowden syndrome from a cohort of 154 European individuals with deleterious germline PTEN mutations. In particular, this individual was affected with mucocutaneous lesions, oral mucosal papillomatosis, macrocephaly and gastrointestinal polyps (Bubien V et al. J Med Genet. 2013 Apr;50(4):255-63). In addition to the clinical data presented in the literature, since alterations that disrupt the canonical splice donor site are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Labcorp Genetics (formerly Invitae), Labcorp RCV003509500 SCV004295311 pathogenic PTEN hamartoma tumor syndrome 2023-04-19 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 167550). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with clinical features of PTEN hamartoma tumor syndrome (PHTS) (PMID: 15372512, 23335809, 30528446). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the PTEN gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675).

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.