Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV003441853 | SCV004168968 | pathogenic | not provided | 2023-04-05 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression ability (Kato et al., 2003; Giacomelli et al., 2018; Kotler et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15510160, 20505364, 17724467, 16861262, 12826609, 26619011, 30224644, 29979965, 29070607, 10922393, 29324801, 21356188, 30840781) |
| Myriad Genetics, |
RCV000663307 | SCV004017828 | likely pathogenic | Li-Fraumeni syndrome 1 | 2023-04-11 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. |
| Labcorp Genetics |
RCV000462351 | SCV000545314 | pathogenic | Li-Fraumeni syndrome | 2025-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 205 of the TP53 protein (p.Tyr205Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with sarcoma (PMID: 29070607). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 376686). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). This variant disrupts the p.Tyr205 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10922393, 12826609, 16861262, 17724467, 20505364, 21356188, 29324801, 29979965, 30224644). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Counsyl | RCV000663307 | SCV000786563 | uncertain significance | Li-Fraumeni syndrome 1 | 2018-05-23 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |