ClinVar Miner

Submissions for variant NM_001304718.2(PTEN):c.-689_-688del (rs121913290)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215567 SCV000275559 pathogenic Hereditary cancer-predisposing syndrome 2015-05-04 criteria provided, single submitter clinical testing The c.17_18delAA mutation, located in exon 1 of the PTEN gene, results from a deletion of 2 nucleotides between positions 17 and 18, causing a translational frameshift with a predicted alternate stop codon. This mutation was detected in a patient with Lhermitte-Duclos disease (Zhou et al. Am J Hum Genet 2003 Nov; 73(5): 1191-8). This mutation is also known as 16-17delAA in the published literature. Since frameshifts are typically deleterious in nature, this mutation is interpreted as disease-causing (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med 2008;10:294).
GeneDx RCV000222693 SCV000279972 pathogenic not provided 2018-08-17 criteria provided, single submitter clinical testing The c.17_18delAA pathogenic variant in the PTEN gene causes a frameshift starting with codon Lysine 6, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Lys6ArgfsX4. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Additionally, it was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although this pathogenic variant has not been previously identified in the germline to our knowledge, other frameshift variants have been reported in the PTEN gene in association with PTEN-related disorders (Stenson et al., 2014).
Invitae RCV000804226 SCV000944123 pathogenic PTEN hamartoma tumor syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys6Argfs*4) in the PTEN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with Cowden syndrome and osteosarcoma (PMID: 29496690). ClinVar contains an entry for this variant (Variation ID: 231649). 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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