ClinVar Miner

Submissions for variant NM_001304718.2(PTEN):c.-656_-655del (rs587781912)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000699087 SCV000840481 pathogenic PTEN hamartoma tumor syndrome 2017-10-18 reviewed by expert panel curation PTEN c.50_51delAA (p.Q17RfsX26) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5' to c.1121 (NM_000314.4). PM2: Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 20223021)
Ambry Genetics RCV000130255 SCV000185099 pathogenic Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing
GeneDx RCV000478451 SCV000565441 pathogenic not provided 2015-01-19 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in PTEN is denoted c.50_51delAA at the cDNA level and p.Gln17ArgfsX26 (Q17RfsX26) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TATC[AA]GAGG. The deletion causes a frameshift, which changes a Glutamine to an Arginine at codon 17, and creates a premature stop codon at position 26 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Invitae RCV000699087 SCV000827782 pathogenic PTEN hamartoma tumor syndrome 2018-05-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln17Argfs*26) in the PTEN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587781912, ExAC 0.001%). This variant has been observed in an individual affected with a personal and/or family history of cancer, as well as in a family affected with Cowden syndrome (PMID:  24763289, 20223021). ClinVar contains an entry for this variant (Variation ID: 141654). 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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