Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002391548 | SCV002672696 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-19 | criteria provided, single submitter | clinical testing | The p.P250A variant (also known as c.748C>G), located in coding exon 6 of the TP53 gene, results from a C to G substitution at nucleotide position 748. The proline at codon 250 is replaced by alanine, an amino acid with highly similar properties. This variant is in the DNA binding domain of the TP53 protein and] is reported to have 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 are equivocal about this variant's ability to suppress cell growth (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 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. |
| Baylor Genetics | RCV003464485 | SCV004206234 | uncertain significance | Adrenocortical carcinoma, hereditary | 2023-09-08 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003509731 | SCV004310912 | uncertain significance | Li-Fraumeni syndrome | 2023-07-31 | 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. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 1759142). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 250 of the TP53 protein (p.Pro250Ala). |