Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001063880 | SCV001228744 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with threonine at codon 2194 of the CEP290 protein (p.Ser2194Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine. This variant is present in population databases (rs768539400, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. 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. 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. |