ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1093G>A (p.Glu365Lys) (rs1064793732)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484163 SCV000566894 pathogenic not provided 2015-06-25 criteria provided, single submitter clinical testing The E365K variant in the PIK3CA gene has been reported previously as a de novo variant in anindividual with megalencephaly-capillary malformation (Riviere et al., 2012). The E365K substitution was notobserved in approximately 5900 individuals of European and African American ancestry in the NHLBIExome Sequencing Project, indicating it is not a common benign variant in these populations. The E365Kvariant is a non-conservative amino acid substitution, which is likely to impact secondary protein structureas these residues differ in polarity, charge, size and/or other properties. This substitution occurs at aposition that is conserved across species. In silico analysis is inconsistent in its predictions as to whether ornot the variant is damaging to the protein structure/function. We interpret E365K as a pathogenic variant.
Invitae RCV000798360 SCV000937973 pathogenic Cowden syndrome 2018-08-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 365 of the PIK3CA protein (p.Glu365Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with PIK3CA related overgrowth syndrome and megalencephaly-capillary malformation syndrome (MCAP) (PMID: 27631024, 22729224). It has also been reported in the mosaic state in an individual with MCAP (PMID: 27631024). ClinVar contains an entry for this variant (Variation ID: 419222). Experimental studies have shown that this missense change increases PIK3CA basal kinase activity and lipid binding (PMID: 18829572). For these reasons, this variant has been classified as Pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785369 SCV000923940 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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