ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.287C>T (p.Pro96Leu) (rs1554898074)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522760 SCV000616840 likely pathogenic not provided 2018-05-04 criteria provided, single submitter clinical testing The P96L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. Different missense substitutions at the same position (P96Q, P96R) have been reported in association with PHTS (Bussaglia et al., 2002; Tan et al., 2011). The P96L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P96L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (D92A/E/N, H93R/Y, P95L, I101T) have been reported in the Human Gene Mutation Database in association with PHTS (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000807643 SCV000947708 uncertain significance PTEN hamartoma tumor syndrome 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 96 of the PTEN protein (p.Pro96Leu). 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 not been reported in the literature in individuals with PTEN-related conditions. ClinVar contains an entry for this variant (Variation ID: 449089). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Pro96 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been observed in individuals with PTEN-related conditions (PMID: 11918710, 23470840), which suggests that this may be a clinically significant amino acid residue. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.