Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000513585 | SCV000608803 | uncertain significance | not provided | 2017-06-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000570720 | SCV000672404 | likely benign | Hereditary cancer-predisposing syndrome | 2016-10-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| ARUP Laboratories, |
RCV000513585 | SCV000884717 | uncertain significance | not provided | 2017-08-10 | criteria provided, single submitter | clinical testing | The TP53 c.478A>G;p.Met160Val variant has not been described in the medical literature as a germline variant occurring in an individual with Li-Fraumeni syndrome. The variant has been described as a somatic variant occurring in multiple different tumors (Glebov 1994, Powell 2000, Yokoyama 1998). The variant is not listed in the ClinVar database, but is listed in the dbSNP variant database (rs377274728) with an allele frequency of 0.0004063 percent (1/246128 alleles) in the Genome Aggregation Database. The amino acid at this position is moderately conserved across species, is reported to occur in a DNA binding domain, and has been reported to not function normally in at least one assay (Shiraishi 2004). However, computational algorithms (AlignGVGD, PolyPhen2, SIFT) predict this variant is tolerated. Considering available information, there is not enough evidence to classify this variant with certainty. References: Glebov OK et al. Frequent p53 gene mutations and novel alleles in familial breast cancer. Cancer Res. 1994 Jul 15;54(14):3703-9. Powell B et al. Prognostic significance of mutations to different structural and functional regions of the p53 gene in breast cancer. Clin Cancer Res. 2000 Feb;6(2):443-51. Shi XB et al. A modified yeast assay used on archival samples of localized prostate cancer tissue improves the detection of p53 abnormalities and increases their predictive value. BJU Int. 2004 Nov;94(7):996-1002. Shiraishi K et al. Isolation of temperature-sensitive p53 mutations from a comprehensive missense mutation library. J Biol Chem. 2004 Jan 2;279(1):348-55. Yokoyama N et al. Mutations of p53 in gallbladder carcinomas in high-incidence areas of Japan and Chile. Cancer Epidemiol Biomarkers Prev. 1998 Apr;7(4):297-301. |
| Labcorp Genetics |
RCV001051011 | SCV001215144 | uncertain significance | Li-Fraumeni syndrome | 2024-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 160 of the TP53 protein (p.Met160Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 444396). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function with a negative predictive value of 97.5%. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 29979965, 30224644). 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 | RCV004568658 | SCV005054353 | uncertain significance | Adrenocortical carcinoma, hereditary | 2023-11-15 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV005356043 | SCV005918328 | uncertain significance | Familial cancer of breast; Li-Fraumeni syndrome 1 | 2024-01-23 | criteria provided, single submitter | clinical testing |