Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019890 | SCV001181302 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-14 | criteria provided, single submitter | clinical testing | The p.Q331K variant (also known as c.991C>A), located in coding exon 8 of the TP53 gene, results from a C to A substitution at nucleotide position 991. The glutamine at codon 331 is replaced by lysine, an amino acid with similar properties. This variant is reported to have transactivation similar to wild type in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration remains proficient at growth suppression (Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001233978 | SCV001406600 | uncertain significance | Li-Fraumeni syndrome | 2022-01-28 | 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. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 30224644). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 823553). 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 glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 331 of the TP53 protein (p.Gln331Lys). |
| Genome- |
RCV002290540 | SCV002582866 | uncertain significance | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV001019890 | SCV002583228 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing |