Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clingen PTEN Variant Curation Expert Panel, |
RCV000461085 | SCV000840487 | pathogenic | PTEN hamartoma tumor syndrome | 2020-03-23 | reviewed by expert panel | curation | PTEN c.801+1delG (IVS7+1delG) 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 PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 23335809) |
Invitae | RCV000461085 | SCV000541581 | pathogenic | PTEN hamartoma tumor syndrome | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change affects a splice site in intron 7 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Cowden syndrome (PMID: 11238682, 20712882; Invitae). This variant is also known as c.802delG. ClinVar contains an entry for this variant (Variation ID: 404140). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003449106 | SCV004188786 | likely pathogenic | Cowden syndrome 1 | 2023-09-29 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
BRCAlab, |
RCV003155939 | SCV002589005 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-26 | no assertion criteria provided | clinical testing |