Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001068015 | SCV001233102 | uncertain significance | Wilson disease | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 368 of the ATP7B protein (p.Met368Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Prevention |
RCV003898074 | SCV004717047 | uncertain significance | ATP7B-related condition | 2023-10-30 | criteria provided, single submitter | clinical testing | The ATP7B c.1104G>A variant is predicted to result in the amino acid substitution p.Met368Ile. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Natera, |
RCV001068015 | SCV002087887 | uncertain significance | Wilson disease | 2021-08-16 | no assertion criteria provided | clinical testing |