ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1636C>A (p.Gln546Lys)

dbSNP: rs121913286
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Total submissions: 24
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical and Molecular Genetics, Hospital Universitario La Paz RCV001705592 SCV001934210 pathogenic Segmental undergrowth associated with mainly venous malformation with capillary component 2021-04-06 criteria provided, single submitter clinical testing
GeneDx RCV001762046 SCV001990614 uncertain significance not provided 2019-04-04 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Missense variants in nearby residues reported in the Human Gene Mutation Database in individuals with PIK3CA-related disorders (Stenson et al., 2014); Has not been previously published in association with PIK3CA-related neurodevelopmental disorders to our knowledge; This variant is associated with the following publications: (PMID: 16930767, 19272638, 19394761, 18221484, 26339434, 31536475, 30591517, 25681199, 27307077, 28453743, 29786783, 29985963)
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV001762046 SCV002525576 pathogenic not provided 2021-12-28 criteria provided, single submitter clinical testing This variant has previously been reported in multiple unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 32350708 and others). The p.Gln546Lys variant substitutes the glutamate at position 546 with lysine within the PIK helical domain of the PIK3CA protein (UniProt P42336). This is an activating mutation that results in ligand-independent activation of the PI3K-AKT-mTOR pathway and increased proliferation in vitro (PMID: 26627007).
Genetics and Personalized Medicine Clinic, Tartu University Hospital RCV004698784 SCV005199859 pathogenic Megalencephaly-capillary malformation-polymicrogyria syndrome criteria provided, single submitter clinical testing
OMIM RCV000014639 SCV000034894 pathogenic OVARIAN CANCER, EPITHELIAL, SOMATIC 2004-11-01 no assertion criteria provided literature only
OMIM RCV000014640 SCV000034895 pathogenic Carcinoma of colon 2004-11-01 no assertion criteria provided literature only
Clinical Genomics Laboratory, Washington University in St. Louis RCV000201230 SCV000255987 likely pathogenic PIK3CA related overgrowth syndrome 2014-12-01 no assertion criteria provided clinical testing
Prostate Cancer Research Center, Institute of Biosciences and Medical Technology, University of Tampere RCV000205164 SCV000259003 likely pathogenic Malignant tumor of prostate no assertion criteria provided research
Database of Curated Mutations (DoCM) RCV000430641 SCV000504038 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441825 SCV000504039 pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424106 SCV000504040 pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431780 SCV000504041 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443162 SCV000504042 likely pathogenic Neoplasm of uterine cervix 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421680 SCV000504043 likely pathogenic Medulloblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431921 SCV000504044 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442141 SCV000504045 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425454 SCV000504046 likely pathogenic Prostate adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436582 SCV000504047 pathogenic Ovarian neoplasm 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442123 SCV000504048 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426539 SCV000504049 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436763 SCV000504050 likely pathogenic Uterine carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419967 SCV000504051 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430236 SCV000504052 likely pathogenic Lung carcinoma 2015-07-14 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne RCV000436582 SCV000924153 pathogenic Ovarian neoplasm 2018-12-01 no assertion criteria provided research

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