Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000816526 | SCV000957040 | uncertain significance | Congenital myasthenic syndrome 8 | 2023-08-01 | 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 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. ClinVar contains an entry for this variant (Variation ID: 659505). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. 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 sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 530 of the AGRN protein (p.Arg530His). |
| Ambry Genetics | RCV003243332 | SCV003942085 | uncertain significance | Inborn genetic diseases | 2023-04-18 | criteria provided, single submitter | clinical testing | The c.1589G>A (p.R530H) alteration is located in exon 8 (coding exon 8) of the AGRN gene. This alteration results from a G to A substitution at nucleotide position 1589, causing the arginine (R) at amino acid position 530 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |