Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055065 | SCV001219430 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 84 of the FIG4 protein (p.Ser84Leu). This variant is present in population databases (rs768384237, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FIG4-related conditions. ClinVar contains an entry for this variant (Variation ID: 850812). 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. 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. |
| Ambry Genetics | RCV002429665 | SCV002742018 | uncertain significance | Inborn genetic diseases | 2020-01-10 | criteria provided, single submitter | clinical testing | The p.S84L variant (also known as c.251C>T), located in coding exon 3 of the FIG4 gene, results from a C to T substitution at nucleotide position 251. The serine at codon 84 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well 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. |