Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001942726 | SCV002134786 | uncertain significance | Familial acute necrotizing encephalopathy | 2021-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 755 of the RANBP2 protein (p.Asp755Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. 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 variant has not been reported in the literature in individuals affected with RANBP2-related conditions. 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. 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. |
Ambry Genetics | RCV004040319 | SCV003706997 | uncertain significance | not specified | 2021-07-16 | criteria provided, single submitter | clinical testing | The c.2263G>A (p.D755N) alteration is located in exon 16 (coding exon 16) of the RANBP2 gene. This alteration results from a G to A substitution at nucleotide position 2263, causing the aspartic acid (D) at amino acid position 755 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |