Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000703443 | SCV000832342 | uncertain significance | Wilson disease | 2018-05-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with glutamic acid at codon 1266 of the ATP7B protein (p.Gly1266Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Wilson disease in whom no second allele was reported (PMID: 23235335). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The observation of one or more missense substitutions at this codon (p.Gly1266Arg and p.Gly1266Trp) in affected individuals suggests that this may be a clinically significant residue (PMID: 21610751, 11243728, 22692182, 21832955). 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. |