ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.253+4_253+7del (rs876659695)

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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 RCV000220273 SCV000276425 likely benign Hereditary cancer-predisposing syndrome 2018-12-21 criteria provided, single submitter clinical testing In silico models in agreement (benign);RNA Studies
Invitae RCV000467976 SCV000541542 uncertain significance PTEN hamartoma tumor syndrome 2020-02-26 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the PTEN gene. It does not directly change the encoded amino acid sequence of the PTEN protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 232320). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000486964 SCV000567725 uncertain significance not provided 2018-02-15 criteria provided, single submitter clinical testing This variant is denoted PTEN c.253+4_253+7delGGTA or IVS4+4_IVS4+7delGGTA and consists of a deletion of four nucleotides at the +4 to +7 position in intron 4 of the PTEN gene. The normal sequence with the bases that are deleted in brackets is Ggta[delggta]tgaa, where the capital letter is exonic and lowercase letters are intronic. This variant is not predicted to cause abnormal splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. PTEN c.253+4_253+7delGGTA was not observed in large population cohorts (Lek 2016). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Two of the nucleotides that are deleted are conserved across species. Based on currently available evidence, it is unclear whether PTEN c.253+4_253+7delGGTA is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
PreventionGenetics,PreventionGenetics RCV000486964 SCV000806062 uncertain significance not provided 2017-11-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000220273 SCV000909476 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-04 criteria provided, single submitter clinical testing

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