Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000438400 | SCV000532953 | uncertain significance | not provided | 2016-10-27 | criteria provided, single submitter | clinical testing | The R1233W variant in the AGRN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1233W variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. The R1233W 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 is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R1233W as a variant of uncertain significance. |
Invitae | RCV000551217 | SCV000653920 | uncertain significance | Congenital myasthenic syndrome 8 | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1233 of the AGRN protein (p.Arg1233Trp). This variant is present in population databases (rs147673996, gnomAD 0.02%). 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: 390183). 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 tryptophan 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. |
Ambry Genetics | RCV003168691 | SCV003902010 | uncertain significance | Inborn genetic diseases | 2023-02-28 | criteria provided, single submitter | clinical testing | The c.3697C>T (p.R1233W) alteration is located in exon 22 (coding exon 22) of the AGRN gene. This alteration results from a C to T substitution at nucleotide position 3697, causing the arginine (R) at amino acid position 1233 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |