Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001205453 | SCV001376713 | uncertain significance | Familial acute necrotizing encephalopathy | 2019-05-29 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with tryptophan at codon 181 of the RANBP2 protein (p.Leu181Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. This variant has not been reported in the literature in individuals with RANBP2-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |