Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000580860 | SCV000686294 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000698048 | SCV000826689 | uncertain significance | PTEN hamartoma tumor syndrome | 2023-08-27 | 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: 29785012). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PTEN protein function. ClinVar contains an entry for this variant (Variation ID: 490114). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 209 of the PTEN protein (p.Gly209Arg). |
Ambry Genetics | RCV000580860 | SCV002660796 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-21 | criteria provided, single submitter | clinical testing | The p.G209R variant (also known as c.625G>A), located in coding exon 6 of the PTEN gene, results from a G to A substitution at nucleotide position 625. The glycine at codon 209 is replaced by arginine, an amino acid with dissimilar properties. This alteration has not been reported in 7051 unselected breast cancer patients and with a allele frequency of 0.00036 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). In a massively parallel functional assay using a humanized yeast model, lipid phosphatase activity for this variant was functionally neutral (Mighell TL et al. Am J Hum Genet, 2018 May;102:943-955). This variant also demonstrated wild type-like intracellular protein abundance in a massively parallel functional assay (Matreyek KA et al. Nat Genet, 2018 Jun;50:874-882). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV000698048 | SCV004838570 | uncertain significance | PTEN hamartoma tumor syndrome | 2023-02-10 | criteria provided, single submitter | clinical testing |