Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000217616 | SCV000279859 | uncertain significance | not provided | 2016-02-04 | criteria provided, single submitter | clinical testing | This variant is denoted PTEN c.869T>C at the cDNA level, p.Val290Ala (V290A) at the protein level, and results in the change of a Valine to an Alanine (GTA>GCA). PTEN Val290Ala has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in colorectal cancer (Betge 2015). PTEN Val290Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Valine and Alanine share similar properties, this is considered a conservative amino acid substitution. PTEN Val290Ala occurs at a position where amino acids with properties similar to Valine are tolerated across species and is located in C2 tensin-type domain (Nguyen 2013, Uniprot). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether PTEN Val290Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV001039253 | SCV001202776 | uncertain significance | PTEN hamartoma tumor syndrome | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 290 of the PTEN protein (p.Val290Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. ClinVar contains an entry for this variant (Variation ID: 234815). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect PTEN function (PMID: 29706350). 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. |