Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491234 | SCV000579959 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-03-09 | criteria provided, single submitter | clinical testing | Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Functionally-validated splicing mutation |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000507780 | SCV000602115 | pathogenic | not provided | 2016-06-10 | criteria provided, single submitter | clinical testing | |
| Gene |
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 | 2019-08-21 | 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). Experimental studies have shown that this variant disrupts mRNA splicing (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, |
RCV000515846 | SCV000579228 | pathogenic | Cowden syndrome 1 | 2017-05-26 | no assertion criteria provided | research |