ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.284C>T (p.Pro95Leu) (rs786204856)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000490609 SCV000930116 pathogenic PTEN hamartoma tumor syndrome 2019-06-25 reviewed by expert panel curation PTEN c.284C>T (p.Pro95Leu) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PS3: Phosphatase activity <50% of wild type (PMID 21828076, PMID 29706350) PM2: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (internal laboratory contributor ClinVar Organization ID 26957) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor ClinVar Organization ID 26957)
Herman Laboratory,Nationwide Children's Hospital RCV000490609 SCV000579266 pathogenic PTEN hamartoma tumor syndrome 2017-03-01 criteria provided, single submitter clinical testing
Invitae RCV000490609 SCV000829973 uncertain significance PTEN hamartoma tumor syndrome 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 95 of the PTEN protein (p.Pro95Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Cowden syndrome and/or PTEN hamartoma tumor syndrome (PMID: 21194675, 21659347, 28526761). ClinVar contains an entry for this variant (Variation ID: 189403). Experimental studies have shown that this missense change partially affects PTEN PIP3 phosphatase activity (PMID: 21828076). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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