Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001932765 | SCV002172442 | uncertain significance | Cone-rod dystrophy 13; Leber congenital amaurosis 6 | 2021-02-02 | criteria provided, single submitter | clinical testing | 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 tolerated, 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 RPGRIP1-related conditions. This variant is present in population databases (rs371994477, ExAC 0.01%). This sequence change replaces methionine with threonine at codon 227 of the RPGRIP1 protein (p.Met227Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. |