Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164915 | SCV000215603 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-10 | criteria provided, single submitter | clinical testing | The p.C296R variant (also known as c.886T>C), located in coding exon 8 of the PTEN gene, results from a T to C substitution at nucleotide position 886. The cysteine at codon 296 is replaced by arginine, an amino acid with highly dissimilar properties. This variant was reported in one individual from a congenital vascular anomalies cohort; however, clinical details were limited (Mattassi R et al. J Vasc Surg, 2018 03;67:922-932.e11). In a massively parallel functional assay using a humanized yeast model, lipid phosphatase activity for this variant was considered to be wild-type-like (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 not well 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. |
| Eurofins Ntd Llc |
RCV000180137 | SCV000232524 | uncertain significance | not provided | 2015-04-17 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000164915 | SCV001354512 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-14 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with arginine at codon 296 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. |
| Labcorp Genetics |
RCV001850307 | SCV002135302 | uncertain significance | PTEN hamartoma tumor syndrome | 2024-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 296 of the PTEN protein (p.Cys296Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with vascular malformations or hemangiomas (PMID: 28655553). ClinVar contains an entry for this variant (Variation ID: 185480). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PTEN protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on PTEN function (PMID: 29785012). 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. |
| Baylor Genetics | RCV003462154 | SCV004206677 | uncertain significance | Glioma susceptibility 2 | 2023-08-22 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV005396479 | SCV006059511 | uncertain significance | Macrocephaly-autism syndrome; Familial meningioma; Glioma susceptibility 2; Familial prostate cancer; Cowden syndrome 1 | 2021-08-04 | criteria provided, single submitter | clinical testing |