Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000473420 | SCV000545304 | pathogenic | Li-Fraumeni syndrome | 2019-10-01 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with phenylalanine at codon 238 of the TP53 protein (p.Cys238Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in the germline of individuals with a TP53-related disease, but has been reported as a somatic variant in various human cancers (PMID: 16337994, 20407015, 24590827, 21115975, 26781615, 27179933, 20878954). ClinVar contains an entry for this variant (Variation ID: 376574). Experimental studies have shown that this variant results in significantly decreased transcriptional transactivation activity of the TP53 protein (PMID: 12826609, 20407015, 25691460). In addition, this variant has been classified as a high-risk mutation associated with decreased drug sensitivity in vitro and in vivo (PMID: 25691460, 25504633, 25634208). The cysteine residue at codon 238 is involved in coordinating a zinc ion in the DNA-binding domain of the TP53 protein (PMID: 8023157, 20407015, 22866089). Different amino acid changes at the same codon (p.Cys238Trp and p.Cys238Tyr) have been observed in individuals with a TP53-related disease and classified as pathogenic variants in the Invitae database, indicating that cysteine 238 is critical for proper protein function. For these reasons, this variant has been classified as Pathogenic. |
Database of Curated Mutations |
RCV000439349 | SCV000507701 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422481 | SCV000507702 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432745 | SCV000507703 | likely pathogenic | Uterine Carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440369 | SCV000507704 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422719 | SCV000507705 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433862 | SCV000507706 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442469 | SCV000507707 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427235 | SCV000507708 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433989 | SCV000507709 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444988 | SCV000507710 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427531 | SCV000507711 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435149 | SCV000507712 | likely pathogenic | Neoplasm of uterine cervix | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000417498 | SCV000507713 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425072 | SCV000507714 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435343 | SCV000507715 | likely pathogenic | Chronic lymphocytic leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418555 | SCV000507716 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428817 | SCV000507717 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only |