Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001024288 | SCV001186273 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-02 | criteria provided, single submitter | clinical testing | The p.L186V variant (also known as c.556C>G), located in coding exon 6 of the PTEN gene, results from a C to G substitution at nucleotide position 556. The leucine at codon 186 is replaced by valine, an amino acid with highly similar properties. This variant was reported in a group of 54 unselected breast cancers screened for PTEN mutations (Rhei E et al. Cancer Res. 1997 Sep;57:3657-9). This variant is located in the loop between the phosphatase and C2 domains, and while it showed decreased expression levels when compared to wild type PTEN, indicating potential impact on protein stability, it retained phosphatase activity and did not change PTEN growth suppression in the U87-MG glioblastoma cell line (Georgescu MM et al. Cancer Res. 2000 Dec;60:7033-8). 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 amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001024288 | SCV001341034 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 186 of the PTEN protein. Functional studies in a cell line have reported this variant did not significantly impact PTEN phosphatase or growth suppression activities, but displayed decreased protein expression (PMID: 11156408). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV001862283 | SCV002150577 | uncertain significance | PTEN hamartoma tumor syndrome | 2022-05-30 | criteria provided, single submitter | clinical testing | 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on PTEN function (PMID: 11156408). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 825836). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 186 of the PTEN protein (p.Leu186Val). |