Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV001172963 | SCV001336038 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Ambry Genetics | RCV002451351 | SCV002736913 | uncertain significance | Inborn genetic diseases | 2020-09-14 | criteria provided, single submitter | clinical testing | The p.S776C variant (also known as c.2327C>G), located in coding exon 20 of the FIG4 gene, results from a C to G substitution at nucleotide position 2327. The serine at codon 776 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV002558742 | SCV003295455 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2022-07-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 776 of the FIG4 protein (p.Ser776Cys). This variant is present in population databases (rs760215765, gnomAD 0.03%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 916877). This variant has not been reported in the literature in individuals affected with FIG4-related conditions. |