Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wong Mito Lab, |
RCV000504267 | SCV000598385 | uncertain significance | Mitochondrial DNA depletion syndrome 13 | 2017-08-10 | criteria provided, single submitter | reference population | The NM_012160.4:c.1069A>G (NP_036292.2:p.Asn357Asp) [GRCH38: NC_000006.12:g.98905460T>C] variant in FBXL4 gene is interpretated to be a Uncertain Significance - Conflicting Evidence based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. BP4:Computational evidence/predictors indicate no impact on the FBXL4 structure, function, or protein-protein interaction. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Uncertain Significance - Conflicting Evidence. |
Invitae | RCV001857193 | SCV002207182 | uncertain significance | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FBXL4 protein function. ClinVar contains an entry for this variant (Variation ID: 437681). This variant has not been reported in the literature in individuals affected with FBXL4-related conditions. This variant is present in population databases (rs199540184, gnomAD 0.01%). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 357 of the FBXL4 protein (p.Asn357Asp). 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. |