ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1030G>A (p.Val344Met)

dbSNP: rs1057519942
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485942 SCV000569339 pathogenic not provided 2021-08-28 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21984976, 26226847, 31278258, 26492180, 24573554, 22653804, 25343854, 22102435, 23907151, 27631024, 30167082, 28973083, 29296277, 31568861, 31785789)
Invitae RCV000631216 SCV000752230 pathogenic Cowden syndrome 2021-07-18 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 344 of the PIK3CA protein (p.Val344Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with megalencephaly (PMID: 27631024; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 376498). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,BC Children's and BC Women's Hospitals RCV000767535 SCV000898153 pathogenic Cowden syndrome 5 2018-06-25 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000433184 SCV000507122 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444028 SCV000507123 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423160 SCV000507124 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433868 SCV000507125 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443225 SCV000507126 likely pathogenic Non-Hodgkin lymphoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427369 SCV000507127 likely pathogenic Neoplasm of uterine cervix 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438004 SCV000507128 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443321 SCV000507129 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Center of Human Genetics, Erasme Hospital RCV000852337 SCV000920642 pathogenic Hypertelorism; Megalencephaly, autosomal dominant; Diaphragmatic eventration; Abnormality of the hairline; Intestinal duplication 2019-06-06 no assertion criteria provided clinical testing The c.1030G>A p.(Val344Met) has been identified by our team in a fetus showing megalencephaly, left diaphragmatic eventration, facial dysmorphism (hypertelorism, abnormal hair line implantation) and duplication of distal portion of the small bowel. The variant arose as a de novo event and it was present in several fetal tissues. In addition, the c.1030G>A p.(Val344Met) variant has been previously reported at de novo constitutional state in two patients presenting megalencephaly (Mirzaa et al., 2016; Yeung et al., 2017). Moreover, this variant is listed in the Catalogue of Somatic Mutations in Cancer (COSMIC accession: COSM253279, COSM253280) and found in several types of carcinoma, glioma and angiosarcoma. Moreover, this variant is not present in frequency databases (gnomAD, Exome Variant Server) and several prediction tools (PolyPhen2, SIFT, LRT, MutationTaster, etc) agree to predict this change as deleterious. Overall, the c.1030G>A p.(Val344Met) variant meets our criteria to be classified as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.