ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.323T>C (p.Leu108Pro) (rs1064793243)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479867 SCV000565447 pathogenic not provided 2014-12-01 criteria provided, single submitter clinical testing This pathogenic variant is denoted PTEN c.323T>C at the cDNA level, p.Leu108Pro (L108P) at the protein level, and results in the change of a Leucine to a Proline (CTT>CCT). This variant was observed in a case of early-onset breast cancer and at least two cases exhibiting clinical features consistent with PTEN hamartoma tumor syndrome (PHTS), one case presenting with learning disabilities, macrocephaly, an ovarian tumor and lipomas, and the other with breast cancer, endometrial cancer and ganglioneuromatosis (Banneau 2010, Tan 2007, Ngeow 2013). PTEN Leu108Pro 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. Since Leucine and Proline differ in some properties, this is considered a semi-conservative amino acid substitution. PTEN Leu108Pro occurs at a position that is well conserved across species and is located in the C2 tensin-type domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the current evidence, we consider this variant to be pathogenic.
Ambry Genetics RCV000490832 SCV000579984 likely pathogenic Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing Other strong data supporting pathogenic classification;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000688225 SCV000815828 pathogenic PTEN hamartoma tumor syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 108 of the PTEN protein (p.Leu108Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Cowden syndrome (PMID: 17526801, 23399955, 20712882, 29043291). ClinVar contains an entry for this variant (Variation ID: 418436). Experimental studies have shown that this missense change impairs the regulation of AKT phosphorylation by PTEN protein (PMID: 25527629). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000479867 SCV000692009 pathogenic not provided no assertion criteria provided clinical testing

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