Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000546565 | SCV000652135 | uncertain significance | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease, dominant intermediate E | 2019-07-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 245 of the INF2 protein (p.Leu245Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs765986755, ExAC 0.005%). This variant has not been reported in the literature in individuals with an INF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on INF2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |