Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001035391 | SCV001198716 | uncertain significance | Congenital myasthenic syndrome 8 | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glycine at codon 905 of the AGRN protein (p.Arg905Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs199593375, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. 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. 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. |
Gene |
RCV002469328 | SCV002765344 | uncertain significance | not provided | 2022-06-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |