Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clingen PTEN Variant Curation Expert Panel, |
RCV000758233 | SCV000886870 | likely pathogenic | PTEN hamartoma tumor syndrome | 2020-06-18 | reviewed by expert panel | curation | PTEN c.170T>G (p.Leu57Trp) meets criteria to be classified as likely 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 9256433, 29706350) PM2: Absent in large sequenced populations 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. |
| Ambry Genetics | RCV000165189 | SCV000215901 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-27 | criteria provided, single submitter | clinical testing | The p.L57W variant (also known as c.170T>G), located in coding exon 3 of the PTEN gene, results from a T to G substitution at nucleotide position 170. The leucine at codon 57 is replaced by tryptophan, an amino acid with similar properties. In one in vitro study, this variant was reported to have a severe reduction in phosphatase activity which was similar to the activity of the catalytically inactive PTEN mutant (Myers MP et al. Proc. Natl. Acad. Sci. U.S.A., 1997 Aug;94:9052-7). In a massively parallel functional assay using a humanized yeast model, lipid phosphatase activity for this variant was functionally deficient (Mighell TL et al. Am J Hum Genet, 2018 May;102:943-955). This variant also demonstrated low intracellular protein abundance in a massively parallel functional assay (Matreyek KA et al. Nat Genet, 2018 Jun;50:874-882). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Eurofins Ntd Llc |
RCV000177035 | SCV000228847 | uncertain significance | not provided | 2015-04-16 | criteria provided, single submitter | clinical testing | |
| CZECANCA consortium | RCV003128151 | SCV003804363 | likely pathogenic | Uterine corpus cancer | 2023-02-21 | no assertion criteria provided | clinical testing |