ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.3129G>T (p.Met1043Ile)

dbSNP: rs121913283
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000631214 SCV000752228 pathogenic Cowden syndrome 2021-07-13 criteria provided, single submitter clinical testing This variant has been reported to be de novo in an individual affected with megalencephaly-capillary malformation syndrome (PMID: 22729224). ClinVar contains an entry for this variant (Variation ID: 217292). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 1043 of the PIK3CA protein (p.Met1043Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. Experimental studies have shown that this missense change increases PIK3CA basal kinase activity and lipid binding (PMID: 15930273, 22120714). For these reasons, this variant has been classified as Pathogenic.
Care4Rare-SOLVE, CHEO RCV000201236 SCV003932127 pathogenic PIK3CA related overgrowth syndrome criteria provided, single submitter research
GeneDx RCV003320599 SCV004025748 pathogenic not provided 2023-08-09 criteria provided, single submitter clinical testing De novo variant with confirmed parentage in multiple patients with PIK3CA-related overgrowth and brain malformations spectrum disorder in the published literature (Riviere et al., 2012; Mirzaa et al., 2016) and mosaic variant in a patient with PIK3CA-related overgrowth and brain malformations spectrum disorder referred for genetic testing at GeneDx; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29883676, 26627007, 18628094, 18516290, 27631024, 33745098, 29707142, 29650325, 29453417, 22729224, 25157968, 15930273, 34693559, 22120714, 35468270, 36635288, 37456262, 36468132, Nasomyont[CaseReport], 36710374, 32398863, 35070505, 34638442, 35715244, 35359373, 35154272)
Clinical Genomics Laboratory, Washington University in St. Louis RCV000201236 SCV000255983 pathogenic PIK3CA related overgrowth syndrome 2014-10-18 no assertion criteria provided clinical testing
Database of Curated Mutations (DoCM) RCV000442578 SCV000504942 likely pathogenic Neoplasm of the large intestine 2015-07-14 no assertion criteria provided literature only

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