Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000633347 | SCV000754569 | uncertain significance | Li-Fraumeni syndrome | 2017-08-24 | 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. A different missense substitution at this codon (p.Tyr163Cys) has been determined to be pathogenic (Invitae). This suggests that the tyrosine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. Experimental studies in yeast have shown that this missense change disrupts TP53 transactivation activity (PMID: 12826609). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376679). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with asparagine at codon 163 of the TP53 protein (p.Tyr163Asn). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and asparagine. |
Ambry Genetics | RCV002338982 | SCV002638731 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-05 | criteria provided, single submitter | clinical testing | The p.Y163N variant (also known as c.487T>A), located in coding exon 4 of the TP53 gene, results from a T to A substitution at nucleotide position 487. The tyrosine at codon 163 is replaced by asparagine, an amino acid with dissimilar properties. 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 amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Myriad Genetics, |
RCV004022250 | SCV004932800 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-14 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 10229196, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. |
Database of Curated Mutations |
RCV000439742 | SCV000510071 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422095 | SCV000510072 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428833 | SCV000510073 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439053 | SCV000510074 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421406 | SCV000510075 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431660 | SCV000510076 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444003 | SCV000510077 | likely pathogenic | Small cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424159 | SCV000510078 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434430 | SCV000510079 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443877 | SCV000510080 | likely pathogenic | Brainstem glioma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427021 | SCV000510081 | likely pathogenic | Uterine carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437297 | SCV000510082 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443298 | SCV000510083 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426404 | SCV000510084 | likely pathogenic | Ovarian serous cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only |