Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001041270 | SCV001204873 | uncertain significance | Li-Fraumeni syndrome | 2019-12-08 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TP53-related conditions. 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. This variant has been reported to have conflicting or insufficient data to determine the effect on TP53 protein function (PMID: 12826609). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 373 of the TP53 protein (p.Lys373Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. |
Color Diagnostics, |
RCV003584803 | SCV004359966 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with asparagine at codon 373 of the TP53 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). This variant partially disrupts function in yeast transactivation assays (IARC database; PMID: 12826609). In human cell growth suppression assays, this variant does not disrupt function and does not exhibit a dominant negative effect (PMID: 30224644). 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. |