ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.3131A>G (p.Asn1044Ser)

dbSNP: rs1064793838
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479562 SCV000567156 pathogenic not provided 2015-07-20 criteria provided, single submitter clinical testing The N1044S substitution in the PIK3CA gene has not been reported previously as a pathogenic variantnor as a benign polymorphism, to our knowledge. The N1044S variant was not observed in approximately6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The N1044S variant is a conservativeamino acid substitution and occurs at a position that is conserved across species. In silico analysis isinconsistent in its predictions as to whether or not the variant is damaging to the proteinstructure/function. Missense variants in nearby residues (A1035V, M1043I, H1047Y, G1049S) havebeen reported in the Human Gene Mutation Database in association with megalencephaly-capillarymalformation (Stenson et al., 2014), supporting the functional importance of this region of the protein. Weinterpret N1044S as a pathogenic variant.
Invitae RCV001856831 SCV002158754 pathogenic Cowden syndrome 2022-01-17 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PIK3CA protein function. ClinVar contains an entry for this variant (Variation ID: 419390). This missense change has been observed in individual(s) with PIK3CA-related overgrowth spectrum (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1044 of the PIK3CA protein (p.Asn1044Ser).
Laboratoire de Génétique Moléculaire, CHU Bordeaux RCV000479562 SCV002568843 pathogenic not provided criteria provided, single submitter clinical testing

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