Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001034818 | SCV001198117 | uncertain significance | Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 | 2019-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with lysine at codon 1354 of the ATP7A protein (p.Arg1354Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is not present in population databases (ExAC no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ATP7A-related conditions. |