Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000704312 | SCV000833256 | pathogenic | Li-Fraumeni syndrome | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 205 of the TP53 protein (p.Tyr205Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Li-Fraumeni syndrome (PMID: 10922393, 21356188, 29324801). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 376681). 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. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 16861262, 17724467, 20505364, 29979965, 30224644). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002356520 | SCV002654466 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-02-22 | criteria provided, single submitter | clinical testing | The p.Y205C pathogenic mutation (also known as c.614A>G), located in coding exon 5 of the TP53 gene, results from an A to G substitution at nucleotide position 614. The tyrosine at codon 205 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in families meeting classic Li Fraumeni syndome (LFS) criteria and LFS-like criteria (Portwine C et al. J Med Genet, 2000 Aug;37:E13; Plon SE et al. Cancer Genet, 2011 Jan;204:19-25; Stoltze U et al. PLoS One, 2018 Jan;13:e0190050). Another alteration at the same codon, p.Y205H (c.613T>C), has been detected in a patient meeting Chompret criteria (Ambry internal data). This variant is in the DNA binding domain of the TP53 protein and is reported to have non-functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect (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 has been observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Myriad Genetics, |
RCV004022251 | SCV004933435 | pathogenic | Li-Fraumeni syndrome 1 | 2024-02-15 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965, 7718482, 7761089, 15037740]. This variant is expected to disrupt protein structure [Myriad internal data]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 29324801, 21356188]. |
Database of Curated Mutations |
RCV000430410 | SCV000510113 | likely pathogenic | Uterine carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440667 | SCV000510114 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422980 | SCV000510115 | likely pathogenic | Papillary renal cell carcinoma type 1 | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433236 | SCV000510116 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439980 | SCV000510117 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422077 | SCV000510118 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432320 | SCV000510119 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443687 | SCV000510120 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424901 | SCV000510121 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431652 | SCV000510122 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443828 | SCV000510123 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427749 | SCV000510124 | likely pathogenic | Non-Hodgkin lymphoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437968 | SCV000510125 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442863 | SCV000510126 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427034 | SCV000510127 | likely pathogenic | Ovarian serous cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437254 | SCV000510128 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only |