Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Research Center, |
RCV000714527 | SCV000845223 | uncertain significance | Ataxia - oculomotor apraxia type 4 | 2018-08-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001219834 | SCV001391792 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 351 of the PNKP protein (p.Pro351Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). 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: 587403). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 |
RCV001759432 | SCV001995194 | uncertain significance | not provided | 2019-08-30 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003380704 | SCV004090996 | uncertain significance | Inborn genetic diseases | 2023-08-15 | criteria provided, single submitter | clinical testing | The c.1052C>T (p.P351L) alteration is located in exon 12 (coding exon 11) of the PNKP gene. This alteration results from a C to T substitution at nucleotide position 1052, causing the proline (P) at amino acid position 351 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |