Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000802465 | SCV000942298 | uncertain significance | Familial acute necrotizing encephalopathy | 2019-07-12 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RANBP2-related disease. This sequence change replaces glycine with cysteine at codon 2198 of the RANBP2 protein (p.Gly2198Cys). The glycine residue is weakly conserved and there is a large physicochemical difference between glycine and cysteine. |