ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.3129G>A (p.Met1043Ile) (rs121913283)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155959 SCV000205671 likely pathogenic Non-small cell lung cancer 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 2018-06-01 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with hemimegalencephaly (PMID: 28151489). ClinVar contains an entry for this variant (Variation ID: 179173). Experimental studies have shown that this missense change increases PIK3CA basal kinase activity and lipid binding (PMID: 15930273, 22120714, 17376864). A different variant (c.3129G>T) giving rise to the same protein effect observed here (p.Met1043Ile) has been reported in several individuals affected with megalencephaly-capillary malformation syndrome (PMID: 22729224, 27631024), indicating that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV001526545 SCV001736970 pathogenic Megalencephaly-capillary malformation-polymicrogyria syndrome criteria provided, single submitter research
Genomics and Pathology Services,Washington University in St.Louis RCV000201237 SCV000255989 pathogenic PIK3CA related overgrowth spectrum 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 Neoplasm of the thyroid gland 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 Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only

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