Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001024674 | SCV001186735 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-18 | criteria provided, single submitter | clinical testing | The p.V197G variant (also known as c.590T>G), located in coding exon 5 of the TP53 gene, results from a T to G substitution at nucleotide position 590. The valine at codon 197 is replaced by glycine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation capacity (IARC TP53 database; Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). It is also reported to be deficient at growth suppression in human cell line studies (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. |
Invitae | RCV001241421 | SCV001414435 | uncertain significance | Li-Fraumeni syndrome | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 197 of the TP53 protein (p.Val197Gly). 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: 33818021). ClinVar contains an entry for this variant (Variation ID: 826051). 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. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609). 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. |
Genome- |
RCV001024674 | SCV002582049 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002290552 | SCV002582347 | uncertain significance | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing |