Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563025 | SCV000671710 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-23 | criteria provided, single submitter | clinical testing | The p.E288K variant (also known as c.862G>A), located in coding exon 8 of the PTEN gene, results from a G to A substitution at nucleotide position 862. The glutamic acid at codon 288 is replaced by lysine, an amino acid with similar properties. In a massively parallel functional assay using a humanized yeast model, lipid phosphatase activity for this variant was wild-type-like (Mighell TL et al. Am J Hum Genet, 2018 May;102:943-955). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Fulgent Genetics, |
RCV000764924 | SCV000896087 | uncertain significance | Macrocephaly-autism syndrome; Familial meningioma; Malignant tumor of prostate; VACTERL with hydrocephalus; Glioma susceptibility 2; PTEN hamartoma tumor syndrome; Cowden syndrome 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001214770 | SCV001386473 | uncertain significance | PTEN hamartoma tumor syndrome | 2023-06-14 | criteria provided, single submitter | clinical testing | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 484603). 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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 288 of the PTEN protein (p.Glu288Lys). 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. |
| Color Diagnostics, |
RCV000563025 | SCV002053297 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-30 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 288 of the PTEN protein. To our knowledge, functional studies have not been reported for this variant. 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. |
| All of Us Research Program, |
RCV001214770 | SCV004838584 | uncertain significance | PTEN hamartoma tumor syndrome | 2023-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 288 of the PTEN protein. To our knowledge, functional studies have not been reported for this variant. 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. |