Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000822499 | SCV000963306 | uncertain significance | Cowden syndrome | 2018-08-13 | criteria provided, single submitter | clinical testing | 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 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. This variant has not been reported in the literature in individuals with PIK3CA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 691 of the PIK3CA protein (p.Tyr691Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. |
| Ambry Genetics | RCV002415939 | SCV002729781 | uncertain significance | Inborn genetic diseases | 2022-06-28 | criteria provided, single submitter | clinical testing | The p.Y691C variant (also known as c.2072A>G), located in coding exon 13 of the PIK3CA gene, results from an A to G substitution at nucleotide position 2072. The tyrosine at codon 691 is replaced by cysteine, an amino acid with highly dissimilar properties. 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. |