ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.253+5G>A

dbSNP: rs1554897889
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703616 SCV000832524 likely pathogenic PTEN hamartoma tumor syndrome 2022-11-22 criteria provided, single submitter clinical testing 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. This variant disrupts the c.253+5G nucleotide in the PTEN gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 24375884, 28677221; Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 4 and introduces a premature termination codon (PMID: 28677221). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 427618). This variant has been observed in individual(s) with Cowden syndrome (PMID: 28677221). This variant is not present in population databases (gnomAD no frequency). 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. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000703616 SCV000992359 likely pathogenic PTEN hamartoma tumor syndrome 2019-09-09 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003321636 SCV004026174 likely pathogenic not provided 2022-09-13 criteria provided, single submitter clinical testing PS4_MOD, PM6, PP3, PM2_SUP
Baylor Genetics RCV003464040 SCV004204848 likely pathogenic Glioma susceptibility 2 2022-11-27 criteria provided, single submitter clinical testing
Cancer Genomic Medicine Translational Research Lab, Cleveland Clinic Genomic Medicine Institute RCV000515980 SCV000579232 pathogenic Cowden syndrome 1 2017-05-26 no assertion criteria provided research

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