ClinVar Miner

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

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cancer Genomic Medicine Translational Research Lab,Cleveland Clinic Genomic Medicine Institute RCV000515839 SCV000579231 pathogenic Cowden syndrome 1 2017-05-26 no assertion criteria provided research
Invitae RCV000684984 SCV000812452 pathogenic PTEN hamartoma tumor syndrome 2018-12-28 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 individuals with symptoms of PTEN hamartoma tumor syndrome (PHTS) (PMID: 28677221, 24375884). In addition, this variant has been observed to segregate with disease in a family (Invitae). ClinVar contains an entry for this variant (Variation ID: 427617). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this substitution causes skipping of exon 4, leading to a protein product that is predicted to be absent (PMID: 28677221). 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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