Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001039625 | SCV001203162 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 107 of the FIG4 protein (p.Ile107Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs372854425, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with FIG4-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV002320246 | SCV002609956 | uncertain significance | Inborn genetic diseases | 2022-09-02 | criteria provided, single submitter | clinical testing | The p.I107M variant (also known as c.321T>G), located in coding exon 4 of the FIG4 gene, results from a T to G substitution at nucleotide position 321. The isoleucine at codon 107 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |