Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001894347 | SCV002124196 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2025-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 400 of the PRKDC protein (p.Thr400Arg). This variant is present in population databases (rs201070491, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1358879). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PRKDC protein function with a positive predictive value of 80%. 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 | RCV004039670 | SCV002643080 | uncertain significance | not specified | 2022-09-16 | criteria provided, single submitter | clinical testing | The p.T400R variant (also known as c.1199C>G), located in coding exon 12 of the PRKDC gene, results from a C to G substitution at nucleotide position 1199. The threonine at codon 400 is replaced by arginine, an amino acid with similar properties. This amino acid position is conserved. 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. |