Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000648427 | SCV000770247 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2021-01-29 | 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 PNKP-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with histidine at codon 110 of the PNKP protein (p.Arg110His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. |
| Ambry Genetics | RCV003162957 | SCV003876077 | uncertain significance | Inborn genetic diseases | 2023-01-17 | criteria provided, single submitter | clinical testing | The c.329G>A (p.R110H) alteration is located in exon 4 (coding exon 3) of the PNKP gene. This alteration results from a G to A substitution at nucleotide position 329, causing the arginine (R) at amino acid position 110 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |