Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004134114 | SCV003613056 | uncertain significance | not specified | 2022-04-08 | criteria provided, single submitter | clinical testing | The c.1967T>C (p.I656T) alteration is located in exon 14 (coding exon 14) of the RANBP2 gene. This alteration results from a T to C substitution at nucleotide position 1967, causing the isoleucine (I) at amino acid position 656 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003619813 | SCV004529998 | uncertain significance | Familial acute necrotizing encephalopathy | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 656 of the RANBP2 protein (p.Ile656Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2282483). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. |