Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Diagnostics Laboratory, |
RCV000583201 | SCV006324629 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2025-08-25 | criteria provided, single submitter | clinical testing | PVS1, PM2_Supporting c.949C>T, located in exon 9 of the TP53 gene, is a nonsense variant expected to result in loss of function by premature protein truncation and nonsense-mediated mRNA decay (PVS1). This variant is located in a mutational hotspot and has been reported in multiple types of tumors (PMID: 33758026, cancerhotspots.org, and internal data). It is not present in the population database gnomAD v2.1.1, non-cancer dataset (PM2_Supporting). The SpliceAI algorithm predicts no significant impact on splicing. According to Giacomelli et al. 2018, it resulted in loss of function with no evidence of a dominant negative effect (PMID: 30224644). To our knowledge, no relevant clinical data have been reported for this variant. This variant has been reported in the ClinVar database (5x pathogenic, 2x likely pathogenic), in the LOVD database (1x pathogenic). Based on the currently available evidence, c.949C>T is classified as a likely pathogenic variant according to ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.2.0. |
| Center for Genomic Medicine, |
RCV004669021 | SCV005094378 | oncogenic | Neoplasm | 2025-03-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000615397 | SCV002969083 | pathogenic | Li-Fraumeni syndrome | 2024-06-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln317*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). 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: 450344). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000583201 | SCV002686961 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-06-24 | criteria provided, single submitter | clinical testing | The p.Q317* pathogenic mutation (also known as c.949C>T), located in coding exon 8 of the TP53 gene, results from a C to T substitution at nucleotide position 949. This changes the amino acid from a glutamine to a stop codon within coding exon 8. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Genome- |
RCV002289710 | SCV002583001 | likely pathogenic | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000583201 | SCV002582339 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000615397 | SCV000731540 | pathogenic | Li-Fraumeni syndrome | 2019-03-13 | criteria provided, single submitter | clinical testing | The p.Gln317X variant in TP53 has not been previously reported in individuals with Li-Fraumeni syndrome or in large population studies. This nonsense variant leads to a premature termination codon at position 317, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the TP53 gene is an established disease mechanism in individuals with Li-Fraumeni syndrome. In summary, this variant meets criteria to be classified as pathogenic for Li-Fraumeni syndrome in an autosomal dominant manner based on predicted impact to the protein and absence in controls. |
| Color Diagnostics, |
RCV000583201 | SCV000691666 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-16 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 9 of the TP53 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with early onset bilateral breast cancer (PMID: 33758026; Color Health internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Gene |
RCV000520579 | SCV000618916 | pathogenic | not provided | 2023-03-15 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate evidence for loss of growth suppression ability (Giacomelli et al., 2018); This variant is associated with the following publications: (PMID: 16322298, 18555592, 16000567, 12067251, 23117049, 31447099, 20522432, 35486574, 36269546, 35672466, 34779821, 34188747, 35884448, 36167829, 32817165, 31719099, 30224644, 33758026) |