Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000706956 | SCV000836031 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 335 of the PNKP protein (p.Gly335Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with PNKP-related conditions. 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 serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Fulgent Genetics, |
RCV000765464 | SCV000896755 | uncertain significance | Microcephaly, seizures, and developmental delay; Ataxia - oculomotor apraxia type 4 | 2018-10-31 | criteria provided, single submitter | clinical testing |