ClinVar Miner

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

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433259 SCV000514309 pathogenic not provided 2017-01-12 criteria provided, single submitter clinical testing The c.253+1G>A splice site variant in the PTEN gene has been previously reported in at least two individuals with clinical features suggestive of PTEN-hamartoma tumor syndrome (Heald et al., 2010; Busch et al., 2013). This variant destroys the canonical splice donor site in intron 4, and is expected to cause abnormal gene splicing. Based on currently available evidence, we consider c.253+1G>A to be pathogenic.
Invitae RCV000529512 SCV000645561 likely pathogenic PTEN hamartoma tumor syndrome 2017-07-05 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 in individuals affected with PTEN-related conditions (PMID: 20600018, 21194675, 23470840). ClinVar contains an entry for this variant (Variation ID: 7820). 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). 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.
Ambry Genetics RCV001015856 SCV001176736 pathogenic Hereditary cancer-predisposing syndrome 2019-07-11 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;Well-characterized mutation at same position
OMIM RCV000008266 SCV000028473 pathogenic Endometrial carcinoma 1998-08-15 no assertion criteria provided literature only
Cancer Genomic Medicine Translational Research Lab,Cleveland Clinic Genomic Medicine Institute RCV000516042 SCV000579230 pathogenic Cowden syndrome 1 2017-05-26 no assertion criteria provided research

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