Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000169866 | SCV000222194 | uncertain significance | not provided | 2018-10-25 | criteria provided, single submitter | clinical testing | This variant is denoted PTEN c.206A>G at the cDNA level, p.Asn69Ser (N69S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. PTEN Asn69Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Asparagine and Serine share similar properties, this is considered a conservative amino acid substitution. PTEN Asn69Ser occurs at a position that is conserved across species and is located in the Phosphatase domain (Nguyen 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether PTEN Asn69Ser is pathogenic or benign. |
| Invitae | RCV000466652 | SCV000541579 | uncertain significance | PTEN hamartoma tumor syndrome | 2018-06-01 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 69 of the PTEN protein (p.Asn69Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 189476). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Ambry Genetics | RCV000564472 | SCV000663569 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-10 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
| Color | RCV000564472 | SCV000686281 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-18 | criteria provided, single submitter | clinical testing |