Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000794332 | SCV000933732 | uncertain significance | Familial acute necrotizing encephalopathy | 2018-11-05 | 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 disease. 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. This sequence change replaces alanine with serine at codon 2564 of the RANBP2 protein (p.Ala2564Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. |
| Ambry Genetics | RCV004027482 | SCV004934424 | uncertain significance | not specified | 2022-08-01 | criteria provided, single submitter | clinical testing | The c.7690G>T (p.A2564S) alteration is located in exon 20 (coding exon 20) of the RANBP2 gene. This alteration results from a G to T substitution at nucleotide position 7690, causing the alanine (A) at amino acid position 2564 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |