Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000821530 | SCV000962289 | uncertain significance | Congenital myasthenic syndrome 8 | 2022-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1320 of the AGRN protein (p.Gly1320Arg). This variant is present in population databases (rs780180385, gnomAD 0.08%). 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: 663617). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine 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 | RCV002537506 | SCV003755007 | uncertain significance | Inborn genetic diseases | 2022-05-11 | criteria provided, single submitter | clinical testing | The c.3958G>A (p.G1320R) alteration is located in exon 23 (coding exon 23) of the AGRN gene. This alteration results from a G to A substitution at nucleotide position 3958, causing the glycine (G) at amino acid position 1320 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |