Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001554947 | SCV001776286 | pathogenic | not provided | 2022-04-06 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect on microtubules (Oegema et al., 2015; Zheng et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); 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: 26639658, 32149430, 26130693, 28835377, 32169460, 32573066, 33064843, 20829227) |
Labcorp Genetics |
RCV001554947 | SCV004296444 | uncertain significance | not provided | 2023-06-03 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TUBB3 protein function. ClinVar contains an entry for this variant (Variation ID: 1192771). This missense change has been observed in individual(s) with TUBB3-related conditions (PMID: 26130693, 35032046). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 357 of the TUBB3 protein (p.Pro357Leu). |