ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.253+5G>A (rs1554897889)

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Total submissions: 3
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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 2019-03-05 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 been reported in an individual affected with Cowden syndrome (PMID: 28677221). ClinVar contains an entry for this variant (Variation ID: 416973). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098).Experimental studies have shown that this variant results in exon 4 skipping and is predicted to result in a frameshift, p. Ala72Thrfs*5 (PMID: 28677221). A different variant affecting this nucleotide (c.253+5G>T) has been reported in individuals affected with symptoms of PTEN hamartoma tumor syndrome and has been determined to be likely pathogenic (PMID: 28677221, 24375884, Invitae). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. 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.
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
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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