ClinVar Miner

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

dbSNP: rs121913283
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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155959 SCV000205671 likely pathogenic Non-small cell lung carcinoma 2013-07-19 criteria provided, single submitter clinical testing The Met1043Ile variant has been identified as a somatic change in tumors from mulitple tissues, including endometrium, lung, cervix, urinary tract and large intestine (COSMIC).
Invitae RCV000699681 SCV000828404 pathogenic Cowden syndrome 2022-07-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PIK3CA function (PMID: 15930273, 17376864, 22120714). 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: 179173). This missense change has been observed in individual(s) with hemimegalencephaly (PMID: 28151489). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1043 of the PIK3CA protein (p.Met1043Ile).
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV001526545 SCV001736970 pathogenic Megalencephaly-capillary malformation-polymicrogyria syndrome criteria provided, single submitter research
GeneDx RCV002293423 SCV002586933 pathogenic not provided 2022-10-20 criteria provided, single submitter clinical testing Identified in patients with features of PIK3CA-related overgrowth and brain malformations spectrum disorder referred for genetic testing at GeneDx and in the published literature (Kuentz et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33745098, 31831300, 22120714, 15930273, 26627007, 28151489)
Clinical Genomics Laboratory, Washington University in St. Louis RCV000201237 SCV000255989 pathogenic PIK3CA related overgrowth syndrome 2015-01-20 no assertion criteria provided clinical testing
Database of Curated Mutations (DoCM) RCV000420209 SCV000504931 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430907 SCV000504932 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441596 SCV000504933 likely pathogenic Thyroid tumor 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420901 SCV000504934 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431600 SCV000504935 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438783 SCV000504936 likely pathogenic Adenoid cystic carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423694 SCV000504937 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433967 SCV000504938 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442493 SCV000504939 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426516 SCV000504940 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433300 SCV000504941 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only

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