Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001930887 | SCV002191730 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2021-09-27 | 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with PNKP-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with methionine at codon 490 of the PNKP protein (p.Thr490Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. |