ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.253+1G>T (rs587776667)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cancer Genomic Medicine Translational Research Lab,Cleveland Clinic Genomic Medicine Institute RCV000515902 SCV000579229 pathogenic Cowden syndrome 1 2017-05-26 no assertion criteria provided research
GeneDx RCV000169865 SCV000222193 pathogenic not provided 2017-09-25 criteria provided, single submitter clinical testing This pathogenic variant is denoted PTEN c.253+1G>T or IVS4+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 4 of the PTEN gene. The variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This mutation segregated in a family with a clinical history consistent with Cowden syndrome (Nelen 1997). Based on current evidence, we consider PTEN c.253+1G>T to be pathogenic.
Invitae RCV000645046 SCV000766786 pathogenic PTEN hamartoma tumor syndrome 2018-11-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 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). This variant has been reported to segregate with Cowden disease in a single family (PMID: 9259288). This variant has also been reported in an individual affected with breast cancer (PMID: 26681312) and an individual affected with juvenile polyposis syndrome (PMID: 17873119). ClinVar contains an entry for this variant (Variation ID: 189475). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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). For these reasons, this variant has been classified as Pathogenic.

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