Submissions for variant NM_006218.4(PIK3CA):c.3139C>T (p.His1047Tyr) (rs121913281)

Total submissions: 27

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine	RCV000038675	SCV000062353	pathogenic	Non-small cell lung cancer	2011-03-01	criteria provided, single submitter	clinical testing	This variant has been observed and confirmed as a somatic variant in large intestine, endometrium, breast and ovarian tumors (COSMIC). Somatic PIK3CA variants have been identified in up to 4% of cases of lung cancer (Samuels 2004).
Invitae	RCV000698423	SCV000827084	pathogenic	Cowden syndrome	2018-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces histidine with tyrosine at codon 1047 of the PIK3CA protein (p.His1047Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be mosaic in individuals affected with megalencephaly-capillary malformation syndrome (PMID: 22729224, 27631024). ClinVar contains an entry for this variant (Variation ID: 39705). Experimental studies have shown that this missense change results in increased kinase activity in vitro and in cultured cells (PMID: 17376864). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics	RCV000763508	SCV000894305	pathogenic	Familial cancer of breast; Megalencephaly cutis marmorata telangiectatica congenita; Lung cancer; Congenital macrodactylia; Keratosis, seborrheic; Epidermal nevus; Neoplasm of ovary; Capillary malformation of the lower lip, lymphatic malformation of face and neck, asymmetry of face and limbs, and partial/generalized overgrowth; Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi; Carcinoma of colon; Neoplasm of stomach; Cowden syndrome 5; Hepatocellular carcinoma	2018-10-31	criteria provided, single submitter	clinical testing
OMIM	RCV000032909	SCV000056681	pathogenic	Megalencephaly cutis marmorata telangiectatica congenita	2012-06-24	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000425809	SCV000504943	likely pathogenic	Malignant melanoma of skin	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000436090	SCV000504944	likely pathogenic	Ovarian Serous Cystadenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000418438	SCV000504945	likely pathogenic	Hepatocellular carcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000425119	SCV000504946	likely pathogenic	Adenocarcinoma of stomach	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000435399	SCV000504947	likely pathogenic	Brainstem glioma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000417782	SCV000504948	likely pathogenic	Medulloblastoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000428005	SCV000504949	likely pathogenic	Glioblastoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000441716	SCV000504950	likely pathogenic	Pancreatic adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000420550	SCV000504951	likely pathogenic	Malignant tumor of floor of mouth	2015-07-14	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000430750	SCV000504952	likely pathogenic	Carcinoma of esophagus	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000441028	SCV000504953	likely pathogenic	Neoplasm of the breast	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000423369	SCV000504954	likely pathogenic	Malignant neoplasm of body of uterus	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000433635	SCV000504955	likely pathogenic	Uterine cervical neoplasms	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000440398	SCV000504956	likely pathogenic	Squamous cell carcinoma of the head and neck	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000422744	SCV000504957	likely pathogenic	Adenocarcinoma of prostate	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000432906	SCV000504958	likely pathogenic	Uterine Carcinosarcoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000442782	SCV000504959	likely pathogenic	Renal cell carcinoma, papillary, 1	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000425540	SCV000504960	likely pathogenic	Squamous cell lung carcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000432323	SCV000504961	likely pathogenic	Lung adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000441963	SCV000504962	likely pathogenic	Neoplasm of the large intestine	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000424877	SCV000504963	likely pathogenic	Neoplasm of brain	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000435124	SCV000504964	likely pathogenic	Transitional cell carcinoma of the bladder	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000444680	SCV000504965	likely pathogenic	Adrenocortical carcinoma	2016-05-31	no assertion criteria provided	literature only