Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693311 | SCV000821175 | uncertain significance | Congenital myasthenic syndrome 8 | 2018-04-27 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 417 of the AGRN protein (p.Asp417Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs148420980, ExAC 0.002%). 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |