Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645042 | SCV000766781 | uncertain significance | PTEN hamartoma tumor syndrome | 2019-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 33 of the PTEN protein (p.Ile33Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PTEN-related disease. 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 | RCV001019879 | SCV001181291 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-06 | criteria provided, single submitter | clinical testing | The p.I33T variant (also known as c.98T>C), located in coding exon 2 of the PTEN gene, results from a T to C substitution at nucleotide position 98. The isoleucine at codon 33 is replaced by threonine, an amino acid with similar properties. 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. |