Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001177820 | SCV001342092 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-11 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 235 of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have demonstrated partial, but significant deficits for this variant in transcriptional transactivation, DNA binding, colony formation and cell proliferation assays (PMID: 12826609, 20128691, 25584008, 29979965, 30224644). This variant has been reported in 3 individuals affected with early onset adrenocortical carcinoma in the literature (PMID: 7966399, 25584008, 25925845). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. |
Invitae | RCV001875860 | SCV002146837 | uncertain significance | Li-Fraumeni syndrome | 2023-03-17 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 919580). 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 expected to disrupt TP53 function. This missense change has been observed in individual(s) with childhood adrenocortical carcinoma (PMID: 7966399). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 235 of the TP53 protein (p.Asn235Asp). |