Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000485746 | SCV000573787 | uncertain significance | not provided | 2017-03-07 | criteria provided, single submitter | clinical testing | The R1796H variant in the AGRN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1796H variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1796H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret R1796H as a variant of uncertain significance. |
Invitae | RCV001050714 | SCV001214835 | uncertain significance | Congenital myasthenic syndrome 8 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1796 of the AGRN protein (p.Arg1796His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with AGRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 424015). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |