Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001053371 | SCV001217629 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 270 of the FIG4 protein (p.Thr270Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs762123072, ExAC 0.07%). 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: "Deleterious"; 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 | RCV002416395 | SCV002679110 | uncertain significance | Inborn genetic diseases | 2020-09-02 | criteria provided, single submitter | clinical testing | The p.T270I variant (also known as c.809C>T), located in coding exon 8 of the FIG4 gene, results from a C to T substitution at nucleotide position 809. The threonine at codon 270 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |