Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000797465 | SCV000937023 | uncertain significance | Congenital myasthenic syndrome 8 | 2018-07-30 | criteria provided, single submitter | clinical testing | While this variant is present in population databases (rs747952589), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with valine at codon 279 of the AGRN protein (p.Ala279Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant has not been reported in the literature in individuals with AGRN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |