Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000087172 | SCV005687972 | uncertain significance | not provided | 2024-07-29 | criteria provided, single submitter | clinical testing | 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; This variant is associated with the following publications: (PMID: 25847421, 16173033, 27527004, 28234344, 29979965, 27882345, 28873162, 15510160, 34240179, 33850299, 30224644, 14559903, 18765419, 34308366) |
| Fulgent Genetics, |
RCV005016380 | SCV005651985 | uncertain significance | Adrenocortical carcinoma, hereditary; Familial cancer of breast; Glioma susceptibility 1; Bone osteosarcoma; Li-Fraumeni syndrome 1; Nasopharyngeal carcinoma; Choroid plexus papilloma; Basal cell carcinoma, susceptibility to, 7; Familial pancreatic carcinoma; Hepatocellular carcinoma; Colorectal cancer; Bone marrow failure syndrome 5 | 2024-04-26 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002514536 | SCV003317131 | uncertain significance | Li-Fraumeni syndrome | 2024-05-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 196 of the TP53 protein (p.Arg196Leu). 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: 34308366). ClinVar contains an entry for this variant (Variation ID: 100814). 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 with a positive predictive value of 97.5%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Color Diagnostics, |
RCV001024636 | SCV001735580 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-04 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with leucine at codon 196 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 this variant has a neutral effect on TP53 protein function (PMID: 29979965, 30224644). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Department of Pediatrics, |
RCV001523825 | SCV001478187 | likely pathogenic | Li-Fraumeni syndrome 1 | 2020-12-15 | criteria provided, single submitter | research | |
| Ambry Genetics | RCV001024636 | SCV001186684 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-04 | criteria provided, single submitter | clinical testing | The p.R196L variant (also known as c.587G>T), located in coding exon 5 of the TP53 gene, results from a G to T substitution at nucleotide position 587. The arginine at codon 196 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported as a somatic mutation two times in various tumors, but not as a germline mutation by the IARC TP53 database (Petitjean A et al. IARC TP53 database [version R17, November 2013]. Hum. Mutat. 2007 Jun;28:622-9). 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. |
| Richard Lifton Laboratory, |
RCV000087172 | SCV000155137 | likely pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission from probable-pathogenic to Likely pathogenic. | |
| Richard Lifton Laboratory, |
RCV000087172 | SCV000120034 | uncertain significance | not provided | flagged submission | not provided | Converted during submission from unknown to Uncertain significance. |