Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000631209 | SCV000752223 | uncertain significance | Cowden syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with alanine at codon 650 of the PIK3CA protein (p.Val650Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PIK3CA-related conditions. 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 tolerated. 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 | RCV003302986 | SCV003996617 | uncertain significance | Inborn genetic diseases | 2023-06-07 | criteria provided, single submitter | clinical testing | The p.V650A variant (also known as c.1949T>C), located in coding exon 12 of the PIK3CA gene, results from a T to C substitution at nucleotide position 1949. The valine at codon 650 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |