ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.492+2T>G (rs1554898244)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000790897 SCV000930137 likely pathogenic PTEN hamartoma tumor syndrome 2018-07-25 reviewed by expert panel curation PTEN c.492+2T>G (IVS5+2T>G) meets criteria to be classified as likely 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).
Invitae RCV000790897 SCV000936766 likely pathogenic PTEN hamartoma tumor syndrome 2018-10-30 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the PTEN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individuals with Cowden syndrome and an individual affected with clinical features of PTEN hamartoma tumor syndrome (PMID: 9425889, 11918710). Variants in this splice site are also known as IVS5+1 or IVS5+2 in the literature. ClinVar contains an entry for this variant (Variation ID: 7821). Donor and acceptor splice site variants 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). 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.
OMIM RCV000008267 SCV000028474 pathogenic Cowden syndrome 1 2003-09-01 no assertion criteria provided literature only

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