Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000723658 | SCV000113439 | uncertain significance | not provided | 2013-08-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000464512 | SCV000549898 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 103 of the PNKP protein (p.Thr103Ile). This variant is present in population databases (rs115419706, gnomAD 0.1%). 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: 95482). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine 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. |
Gene |
RCV000723658 | SCV000577235 | uncertain significance | not provided | 2023-05-31 | criteria provided, single submitter | clinical testing | 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; This variant is associated with the following publications: (PMID: 22508754) |
Ambry Genetics | RCV002316251 | SCV000849820 | uncertain significance | Inborn genetic diseases | 2019-02-17 | criteria provided, single submitter | clinical testing | The p.T103I variant (also known as c.308C>T), located in coding exon 3 of the PNKP gene, results from a C to T substitution at nucleotide position 308. The threonine at codon 103 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved on limited sequence alignment; however, isoleucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Mayo Clinic Laboratories, |
RCV000723658 | SCV001713024 | uncertain significance | not provided | 2020-02-04 | criteria provided, single submitter | clinical testing |