Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001225217 | SCV001397458 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2022-06-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FIG4-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 952986). This variant is present in population databases (rs754127221, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 603 of the FIG4 protein (p.Gly603Glu). |
Gene |
RCV001751436 | SCV001995672 | uncertain significance | not provided | 2019-12-10 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |