Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001334683 | SCV001527592 | uncertain significance | Mitochondrial DNA depletion syndrome 13 | 2018-12-06 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Labcorp Genetics |
RCV001865815 | SCV002123823 | uncertain significance | not provided | 2021-06-08 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with FBXL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1032551). 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 FBXL4 protein function. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 180 of the FBXL4 protein (p.Pro180Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |