Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001368544 | SCV001564941 | uncertain significance | Familial acute necrotizing encephalopathy | 2020-08-06 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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. This variant has not been reported in the literature in individuals with RANBP2-related conditions. This variant is present in population databases (rs776783992, ExAC 0.009%). This sequence change replaces threonine with alanine at codon 1742 of the RANBP2 protein (p.Thr1742Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. |
| Ambry Genetics | RCV004037048 | SCV003990300 | uncertain significance | not specified | 2023-06-05 | criteria provided, single submitter | clinical testing | The c.5224A>G (p.T1742A) alteration is located in exon 20 (coding exon 20) of the RANBP2 gene. This alteration results from a A to G substitution at nucleotide position 5224, causing the threonine (T) at amino acid position 1742 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |