Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001172158 | SCV001335125 | pathogenic | not provided | 2020-02-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002502454 | SCV002810301 | pathogenic | Familial cancer of breast; Megalencephaly-capillary malformation-polymicrogyria syndrome; Congenital macrodactylia; Seborrheic keratosis; Epidermal nevus; Neoplasm of ovary; CLAPO syndrome; CLOVES syndrome; Cowden syndrome 5; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Lung cancer | 2022-03-23 | criteria provided, single submitter | clinical testing | |
Clinical Genomics Laboratory, |
RCV003458198 | SCV004176944 | pathogenic | PIK3CA related overgrowth syndrome | 2023-10-27 | criteria provided, single submitter | clinical testing | The PIK3CA c.1035T>A (p.Asn345Lys) variant was identified at an allelic fraction consistent with somatic origin. This variant has been reported in at least three individuals affected with PROS disorders (Parker VER et al., PMID: 30270358, Tian W et al., PMID: 35122151; McNulty SN et al., PMID: 31585106). The PIK3CA c.1035T>A (p.Asn345Lys) variant has been reported in numerous cases in the cancer database COSMIC (COSMIC Genomic Mutation ID COSV55873276 ) and it has been reported in the ClinVar database as pathogenic by two submitters (ClinVar ID: 376050). This variant is absent from the general population (gnomAD V.3.1.2), indicating it is not a common variant. The PIK3CA c.1035T>A (p.Asn345Lys) variant is considered to be a strong oncogenic variant (Gymnopoulos M et al., PMID: 17376864) and resides in the C2 catalytic subunit of PIK3CA that is defined as a critical functional domain (Madsen R et al., PMID: 30197175; Keppler-Noreuil KM et al., PMID: 25557259). Functional in vitro studies show that this variant leads to autonomous phosphorylation of AKT and activation of the downstream AKT-mTOR signaling, indicating that this variant impacts protein function (Gymnopoulos M et al., PMID: 17376864). The PIK3CA gene is defined by the ClinGen Brain Malformations expert panel as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (Lai A et al. PMID: 35997716). Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and gene-specific practices from the ClinGen Criteria Specification Registry PIK3CA c.1035T>A (p.Asn345Lys) variant is classified as pathogenic. |
Database of Curated Mutations |
RCV000434766 | SCV000504918 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442207 | SCV000504919 | likely pathogenic | Prostate adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424744 | SCV000504920 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435436 | SCV000504921 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442343 | SCV000504922 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425343 | SCV000504923 | likely pathogenic | Uterine carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436059 | SCV000504924 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418844 | SCV000504925 | likely pathogenic | Adenoid cystic carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426096 | SCV000504926 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436776 | SCV000504927 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
MAGI's Lab - |
RCV001327959 | SCV001437635 | pathogenic | Abnormal cardiovascular system morphology | no assertion criteria provided | provider interpretation |