Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001337578 | SCV001531184 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2020-08-10 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PNKP-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tryptophan at codon 516 of the PNKP protein (p.Cys516Trp). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tryptophan. 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. |