Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000425529 | SCV000533733 | uncertain significance | not provided | 2016-11-18 | criteria provided, single submitter | clinical testing | The R884C variant in the AGRN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R884C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R884C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R884C as a variant of uncertain significance. |
Invitae | RCV001851071 | SCV002136646 | uncertain significance | Congenital myasthenic syndrome 8 | 2022-11-08 | criteria provided, single submitter | clinical testing | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 390809). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. This variant is present in population databases (rs539990009, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 884 of the AGRN protein (p.Arg884Cys). |