Submissions for variant NM_006218.4(PIK3CA):c.1637A>G (p.Gln546Arg)

dbSNP: rs397517201

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine	RCV000038672	SCV000062350	pathogenic	Neoplasm of ovary	2010-08-10	criteria provided, single submitter	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002254273	SCV002525570	pathogenic	not provided	2021-02-04	criteria provided, single submitter	clinical testing	This variant has previously been reported in multiple unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 25681199, PMID: 31585106). Phenotypic information was limited in the majority of cases, but one individual had a clinical diagnosis of Fibro-Adipose Vascular Anomaly (FAVA) (PMID: 25681199). PIK3CA variants associated with PROS, including this patient's alteration, overlap those reported as oncogenic variants found in multiple tumor types (cBioPortal and NCI's Genomic Data Commons cancer databases). The p.Gln546Arg replaces the glutamine at codon 546 with arginine within the helical domain of the PIK3CA protein (UniProt P42336). Experimental studies have demonstrated that the p.Gln546Arg variant causes overactivation of the PI3K/AKT/mTOR pathway and increased proliferation in vitro (PMID: 2662700).
Database of Curated Mutations (DoCM)	RCV000439651	SCV000504079	pathogenic	Breast neoplasm	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000422863	SCV000504080	pathogenic	Neoplasm of the large intestine	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000433168	SCV000504081	likely pathogenic	Glioblastoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000440779	SCV000504082	likely pathogenic	Malignant melanoma of skin	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000423116	SCV000504083	likely pathogenic	Malignant neoplasm of body of uterus	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000434246	SCV000504084	likely pathogenic	Prostate adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000443308	SCV000504085	likely pathogenic	Neoplasm of brain	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000427826	SCV000504086	likely pathogenic	Uterine carcinosarcoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000434598	SCV000504087	likely pathogenic	Squamous cell carcinoma of the head and neck	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000442332	SCV000504088	likely pathogenic	Medulloblastoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000424486	SCV000504089	likely pathogenic	Transitional cell carcinoma of the bladder	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000435640	SCV000504090	likely pathogenic	Gastric adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000417964	SCV000504091	likely pathogenic	Neoplasm of uterine cervix	2016-05-31	no assertion criteria provided	literature only
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000038672	SCV000923960	likely pathogenic	Neoplasm of ovary	2018-12-01	no assertion criteria provided	research
MAGI's Lab - Research,MAGI Group	RCV001327965	SCV001437641	pathogenic	Abnormality of cardiovascular system morphology		no assertion criteria provided	provider interpretation