Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000803512 | SCV000943390 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2018-10-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with PNKP-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 358 of the PNKP protein (p.Arg358Lys). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and lysine. 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. 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. |