Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000696471 | SCV000825034 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2022-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 374 of the PNKP protein (p.Pro374Ser). This variant is present in population databases (rs760583725, gnomAD 0.002%). 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: 574517). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
Gene |
RCV001771969 | SCV001992515 | uncertain significance | not provided | 2022-06-22 | 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 |
Ambry Genetics | RCV002440483 | SCV002748395 | uncertain significance | Inborn genetic diseases | 2019-11-01 | criteria provided, single submitter | clinical testing | The p.P374S variant (also known as c.1120C>T), located in coding exon 11 of the PNKP gene, results from a C to T substitution at nucleotide position 1120. The proline at codon 374 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |