Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688366 | SCV000815974 | uncertain significance | Li-Fraumeni syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 376578). This missense change has been observed in individual(s) with breast or ovarian cancer (PMID: 29470806). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 242 of the TP53 protein (p.Cys242Phe). |
Ambry Genetics | RCV002379285 | SCV002671484 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-13 | criteria provided, single submitter | clinical testing | The p.C242F pathogenic mutation (also known as c.725G>T), located in coding exon 6 of the TP53 gene, results from a G to T substitution at nucleotide position 725. The cysteine at codon 242 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration has been identified in an Indian breast/ovarian cancer cohort (Singh J et al. Breast Cancer Res. Treat., 2018 Jul;170:189-196). This alteration has been reported as a germline alteration and as a somatic alteration in various tumors by the IARC TP53 database (Bouaoun L et al. IARC TP53 database [version 20, July 2019]. Hum. Mutat. 2016 Sep;37:865-76). This alteration is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Studies conducted in human cell lines are equivocal about this variant's ability to suppress cell growth (Kotler E et al. Mol. Cell 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This alteration is located in the functionally critical DNA binding domain, and it is one of four amino acid residues required for zinc binding and protein stabilization (Cho Y et al. Science, 1994 Jul;265:346-55). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Database of Curated Mutations |
RCV000433671 | SCV000507769 | likely pathogenic | B-cell chronic lymphocytic leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442449 | SCV000507770 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427153 | SCV000507771 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438269 | SCV000507772 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442305 | SCV000507773 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424746 | SCV000507774 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435022 | SCV000507775 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000417879 | SCV000507776 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425032 | SCV000507777 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435743 | SCV000507778 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418512 | SCV000507779 | likely pathogenic | Uterine carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000785473 | SCV000924045 | likely pathogenic | Neoplasm of ovary | 2018-12-01 | no assertion criteria provided | research |