Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001805037 | SCV002052524 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-02-21 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with cysteine at codon 270 of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that the mutant is defective in transcriptional transactivation of TP53 target genes, displays loss of function and dominant negative activity in human cell growth suppression assays, and is non-functional in human cell proliferation assays (PMID: 12826609, 29979965, 30224644). This variant has been observed germline in two individuals suspected of having Li-Fraumeni syndrome (PMID: 32817165). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. |
Gene |
RCV002508212 | SCV002817846 | likely pathogenic | not provided | 2022-12-28 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression ability, and dominant negative effect (Kato et al., 2003; Dearth et al., 2007; Giacomelli et al., 2018; Kotler et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in the literature in families with Li-Fraumeni syndrome (Gao et al., 2020); This variant is associated with the following publications: (PMID: 15510160, 26619011, 32817165, 32358561, 29979965, 28160562, 30808373, 27662657, 16861262, 15308588, 30224644, 12826609) |
Labcorp Genetics |
RCV002524696 | SCV003317121 | uncertain significance | Li-Fraumeni syndrome | 2022-03-26 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 270 of the TP53 protein (p.Phe270Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 32817165). ClinVar contains an entry for this variant (Variation ID: 376597). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. 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. |
Baylor Genetics | RCV003470375 | SCV004206230 | likely pathogenic | Adrenocortical carcinoma, hereditary | 2023-09-22 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV004022213 | SCV004932392 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-20 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 7651740, 10713666, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. |
Database of Curated Mutations |
RCV000441020 | SCV000508116 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424190 | SCV000508117 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434574 | SCV000508118 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440467 | SCV000508119 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422786 | SCV000508120 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433925 | SCV000508121 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443933 | SCV000508122 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422121 | SCV000508123 | likely pathogenic | Ovarian serous cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432351 | SCV000508124 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only |