Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001370743 | SCV001567275 | uncertain significance | Familial acute necrotizing encephalopathy | 2020-01-18 | criteria provided, single submitter | clinical testing | This variant has been observed in an individual with acute hemorrhagic encephalomyelitis and sickle cell disease (PMID: 29593631). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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 lysine with glutamic acid at codon 1665 of the RANBP2 protein (p.Lys1665Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. |
| Prevention |
RCV003898353 | SCV004714060 | uncertain significance | RANBP2-related condition | 2023-12-07 | criteria provided, single submitter | clinical testing | The RANBP2 c.4993A>G variant is predicted to result in the amino acid substitution p.Lys1665Glu. This variant was reported in the heterozygous state in an individual with sickle cell disease who later presented with an acquired demyelinating syndrome (Alawadhi et al. 2018. PubMed ID: 29593631). This variant is reported in 0.020% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |