Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001317864 | SCV001508542 | uncertain significance | Familial acute necrotizing encephalopathy | 2020-06-02 | criteria provided, single submitter | clinical testing | 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 conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with lysine at codon 204 of the RANBP2 protein (p.Asn204Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. |
| Ambry Genetics | RCV003263949 | SCV003967650 | uncertain significance | Inborn genetic diseases | 2023-04-11 | criteria provided, single submitter | clinical testing | The c.612T>G (p.N204K) alteration is located in exon 5 (coding exon 5) of the RANBP2 gene. This alteration results from a T to G substitution at nucleotide position 612, causing the asparagine (N) at amino acid position 204 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |