Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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. |
Genomics and Pathology Services, |
RCV000201237 | SCV000255989 | pathogenic | PIK3CA related overgrowth spectrum | 2015-01-20 | no assertion criteria provided | clinical testing | |
Database of Curated Mutations |
RCV000420209 | SCV000504931 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430907 | SCV000504932 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000441596 | SCV000504933 | likely pathogenic | Neoplasm of the thyroid gland | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420901 | SCV000504934 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431600 | SCV000504935 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438783 | SCV000504936 | likely pathogenic | Adenoid cystic carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
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 |
RCV000433967 | SCV000504938 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442493 | SCV000504939 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426516 | SCV000504940 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433300 | SCV000504941 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only |