Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649968 | SCV000771805 | uncertain significance | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease, dominant intermediate E | 2017-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with histidine at codon 591 of the INF2 protein (p.Asp591His). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs369421697, ExAC 0.005%). This variant has not been reported in the literature in individuals with INF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |