Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute for Genomic Medicine |
RCV006254267 | SCV007104853 | tier i - strong | Diffuse midline glioma, H3 K27M-mutant | 2022-11-09 | criteria provided, single submitter | clinical testing | Variant has Tier I (strong) clinical significance as a diagnostic inclusion criterion in diffuse midline glioma, H3 K27M-mutant, based on the following evidence: 1) Documented in one or more cancer databases (e.g., St. Jude Pecan, COSMIC, CIViC, OncoKB). 2) Appears in one or more well-established professional guidelines (e.g., World Health Organization [WHO]; National Comprehensive Cancer Network [NCCN]) as providing diagnostic, prognostic, or therapeutic information. 3) Information in the literature supports potential biologic effect of variant. 4) Diagnostic for a specific tumor type/classification based on well-powered studies with expert-level consensus (Evidence Level B; PMIDs: 24705251, 22661320, 34796414, 33433639). |
| Myriad Genetics, |
RCV004035219 | SCV004931798 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-14 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant is expected to disrupt protein structure [Myriad internal data]. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 29070607]. |
| Labcorp Genetics |
RCV001326770 | SCV001517819 | pathogenic | Li-Fraumeni syndrome | 2026-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 159 of the TP53 protein (p.Ala159Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Li Fraumeni syndrome and/or clinical features of Li-Fraumeni syndrome (PMID: 27545002, 29070607, 32658383). ClinVar contains an entry for this variant (Variation ID: 1026335). 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). This variant disrupts the p.Ala159 amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in individuals with TP53-related conditions (internal data), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Laboratory of Virology, |
RCV003483816 | SCV004232138 | uncertain significance | Prostate cancer, hereditary, 1 | 2024-01-01 | no assertion criteria provided | clinical testing |