Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001065980 | SCV001230973 | uncertain significance | not provided | 2021-01-12 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs763230559, ExAC 0.01%). This sequence change replaces proline with threonine at codon 2043 of the ABCA4 protein (p.Pro2043Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant has not been reported in the literature in individuals with ABCA4-related conditions. 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. |