Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001040749 | SCV001204338 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 714 of the FIG4 protein (p.Thr714Ile). This variant is present in population databases (rs146689226, gnomAD 0.01%). 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: 839068). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. |
| Molecular Genetics Laboratory, |
RCV001172956 | SCV001336031 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Ambry Genetics | RCV002427505 | SCV002730092 | uncertain significance | Inborn genetic diseases | 2022-08-15 | criteria provided, single submitter | clinical testing | The p.T714I variant (also known as c.2141C>T), located in coding exon 19 of the FIG4 gene, results from a C to T substitution at nucleotide position 2141. The threonine at codon 714 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly 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. |