Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000633400 | SCV000754622 | uncertain significance | Li-Fraumeni syndrome | 2023-07-10 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 195 of the TP53 protein (p.Ile195Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 376620). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TP53 function (PMID: 12826609). 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. |
Ambry Genetics | RCV002356516 | SCV002650266 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-28 | criteria provided, single submitter | clinical testing | The p.I195M variant (also known as c.585C>G), located in coding exon 5 of the TP53 gene, results from a C to G substitution at nucleotide position 585. The isoleucine at codon 195 is replaced by methionine, an amino acid with highly similar properties. This variant (is in the DNA binding domain of the TP53 protein and) is reported to have reduced transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Additional studies conducted in human cell lines indicate this alteration has no dominant negative effect and remains proficient at growth suppression (Kotler E et al. Mol. Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Database of Curated Mutations |
RCV000419550 | SCV000508672 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000429834 | SCV000508673 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436566 | SCV000508674 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418858 | SCV000508675 | likely pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000429158 | SCV000508676 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439382 | SCV000508677 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421371 | SCV000508678 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428127 | SCV000508679 | likely pathogenic | Uterine carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438380 | SCV000508680 | likely pathogenic | B-cell chronic lymphocytic leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424140 | SCV000508681 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434462 | SCV000508682 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442092 | SCV000508683 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423525 | SCV000508684 | likely pathogenic | Ovarian serous cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433822 | SCV000508685 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442140 | SCV000508686 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426409 | SCV000508687 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only |