Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000793378 | SCV000932726 | uncertain significance | Menkes kinky-hair syndrome; Cutis laxa, X-linked; Distal spinal muscular atrophy, X-linked 3 | 2019-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 69 of the ATP7A protein (p.Met69Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs782290331, ExAC 0.004%). This variant has not been reported in the literature in individuals with ATP7A-related disease. 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |