Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
RCV000767535 | SCV000898153 | pathogenic | Cowden syndrome 5 | 2018-06-25 | criteria provided, single submitter | clinical testing | |
Database of Curated Mutations |
RCV000433184 | SCV000507122 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444028 | SCV000507123 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423160 | SCV000507124 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
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 |
RCV000443225 | SCV000507126 | likely pathogenic | Non-Hodgkin lymphoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427369 | SCV000507127 | likely pathogenic | Neoplasm of uterine cervix | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438004 | SCV000507128 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443321 | SCV000507129 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Center of Human Genetics, |
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. |