ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.210-1G>A (rs1114167621)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491234 SCV000579959 pathogenic Hereditary cancer-predisposing syndrome 2014-11-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507780 SCV000602115 pathogenic not provided 2016-06-10 criteria provided, single submitter clinical testing
GeneDx RCV000507780 SCV000616839 pathogenic not provided 2018-05-04 criteria provided, single submitter clinical testing This variant is denoted PTEN c.210-1G>A or IVS3-1G>A and consists of a G>A nucleotide substitution at the -1 position of intron 3 of the PTEN gene. This variant destroys a canonical splice acceptor site and has been demonstrated by RT-PCR studies to cause abnormal gene splicing, leading to skipping of exon 4 and subsequent nonsense-mediated mRNA decay (Celebi 2000, Agrawal 2005, Chen 2017). This variant has been reported in several individuals with features of PTEN Hamartoma Tumor syndrome, with at least one de novo observation (Celebi 2000, Mester 2012, Ngeow 2012, Iskandarli 2016, Chen 2017). Based on the current evidence, we consider this variant to be pathogenic.
Invitae RCV000645050 SCV000766790 pathogenic PTEN hamartoma tumor syndrome 2017-12-27 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 3 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 in an individual affected with Cowden syndrome (PMID: 11071384), and in a cohort of individuals with thyroid cancer and Cowden or Cowden-Like syndrome (PMID: 21956414). ClinVar contains an entry for this variant (Variation ID: 427616). Reverse transcription polymerase chain reaction (RT-PCR) analysis has shown that this sequence change disrupts the 3’ (acceptor) splice site resulting in skipping of exon 4 (PMID: 11071384). 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.
Cancer Genomic Medicine Translational Research Lab,Cleveland Clinic Genomic Medicine Institute RCV000515846 SCV000579228 pathogenic Cowden syndrome 1 2017-05-26 no assertion criteria provided research

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