Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001339841 | SCV001533616 | uncertain significance | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 308 of the IL6R protein (p.Pro308Leu). This variant is present in population databases (rs148682883, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with IL6R-related conditions. ClinVar contains an entry for this variant (Variation ID: 1036785). 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. Experimental studies have shown that this missense change affects IL6R function (PMID: 8467812). 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. |
Johns Hopkins Genomics, |
RCV001353358 | SCV001548512 | uncertain significance | Hyper-IgE recurrent infection syndrome 5, autosomal recessive | 2021-03-23 | criteria provided, single submitter | clinical testing |