ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)

dbSNP: rs1057519925
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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Undiagnosed Diseases Network,NIH RCV000991209 SCV001142587 pathogenic Megalencephaly-capillary malformation-polymicrogyria syndrome 2019-05-06 criteria provided, single submitter clinical testing
Baylor Genetics RCV000991209 SCV001521015 pathogenic Megalencephaly-capillary malformation-polymicrogyria syndrome 2020-06-25 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV001526693 SCV001737114 pathogenic CLOVES syndrome criteria provided, single submitter clinical testing
GeneDx RCV001775789 SCV002013346 pathogenic not provided 2021-05-17 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: increased phosphorylation of AKT on serine 473 (Rudd et al., 2011); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23352210, 29759595, 21266528, 26619011, 21531001, 27834349, 27631024, 30063105, 27037860, 31263565)
Invitae RCV001861479 SCV002247469 pathogenic Cowden syndrome 2021-10-14 criteria provided, single submitter clinical testing
Daryl Scott Lab,Baylor College of Medicine RCV002244865 SCV002515365 pathogenic PIK3CA-related disorder 2022-02-01 criteria provided, single submitter clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV001775789 SCV002525708 pathogenic not provided 2021-08-26 criteria provided, single submitter clinical testing This variant has previously been reported in multiple unrelated individuals with a molecular diagnosis of PROS, including those with reported overgrowth and macrodactyly (PMID: 27631024, PMID: 31263565). The p.Glu453Lys variant substitutes the glutamic acid at position 453 with lysine within the C2 phosphatidylinositol 3-kinase domain of the PIK3CA protein (UniProt P42336, aa# 330-487). This is a recurrent hotspot. PIK3CA variants associated with PROS overlap those reported as oncogenic variants found in multiple tumor types (COSMIC and cBioPortal Databases)
Database of Curated Mutations (DoCM) RCV000430361 SCV000506827 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440626 SCV000506828 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422944 SCV000506829 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433137 SCV000506830 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443243 SCV000506831 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423945 SCV000506832 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434215 SCV000506833 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442682 SCV000506834 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425038 SCV000506835 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435327 SCV000506836 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne RCV000785580 SCV000924154 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research
MAGI's Lab - Research,MAGI Group RCV001327961 SCV001437637 pathogenic Abnormality of cardiovascular system morphology no assertion criteria provided provider interpretation

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