Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489945 | SCV000576834 | uncertain significance | not provided | 2023-03-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Labcorp Genetics |
RCV000648426 | SCV000770246 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2022-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 466 of the PNKP protein (p.Met466Thr). This variant is present in population databases (rs145886749, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PNKP-related conditions. ClinVar contains an entry for this variant (Variation ID: 426407). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PNKP 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. |
Ambry Genetics | RCV002318595 | SCV000851061 | uncertain significance | Inborn genetic diseases | 2021-08-16 | criteria provided, single submitter | clinical testing | The c.1397T>C (p.M466T) alteration is located in exon 16 (coding exon 15) of the PNKP gene. This alteration results from a T to C substitution at nucleotide position 1397, causing the methionine (M) at amino acid position 466 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV000489945 | SCV003811228 | uncertain significance | not provided | 2021-01-09 | criteria provided, single submitter | clinical testing |