ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.1A>G (p.Met1Val) (rs1554890324)

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
ClinGen PTEN Variant Curation Expert Panel RCV000706088 SCV001244242 pathogenic PTEN hamartoma tumor syndrome 2019-11-22 reviewed by expert panel curation PTEN c.1A>G (p.M1?) meets criteria to be classified as 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). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5' to c.1121 (NM_000314.4). PM2: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 29752200) PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 29752200, 28774669; internal laboratory contributor ClinVar Organization ID: 26957)
Ambry Genetics RCV000572416 SCV000671706 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-08 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000706088 SCV000835120 likely pathogenic PTEN hamartoma tumor syndrome 2019-09-10 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the PTEN mRNA. The next in-frame methionine is located at codon 35. This variant is not present in population databases (ExAC no frequency). Disruption of the Met1 initiator codon has been observed in the literature in individuals affected with PTEN-related disease (PMID: 28774669, 29752200, 27157322, 28600779, 23695273). ClinVar contains an entry for this variant (Variation ID: 484600). A missense variant (p.Asp24Gly) located upstream of the next in-frame methionine has been determined to be pathogenic (PMID: 21194675, 22503188, 24498881, Invitae). This indicates that the N-terminal region is critical for PTEN protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.