Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000525233 | SCV000626811 | uncertain significance | Cowden syndrome | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 583 of the PIK3CA protein (p.Met583Val). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 456533). This variant has not been reported in the literature in individuals affected with PIK3CA-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Ambry Genetics | RCV002404376 | SCV002711377 | uncertain significance | Inborn genetic diseases | 2021-09-18 | criteria provided, single submitter | clinical testing | The p.M583V variant (also known as c.1747A>G) is located in coding exon 11 of the PIK3CA gene. The methionine at codon 583 is replaced by valine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 11. This amino acid position is conserved. 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. |