Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001038609 | SCV001202088 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2022-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 420 of the PRKDC protein (p.Val420Ile). This variant is present in population databases (rs55925466, gnomAD 0.01%). 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: 837309). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; 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. |
| Ambry Genetics | RCV003160244 | SCV003864519 | uncertain significance | Inborn genetic diseases | 2022-12-07 | criteria provided, single submitter | clinical testing | The p.V420I variant (also known as c.1258G>A), located in coding exon 12 of the PRKDC gene, results from a G to A substitution at nucleotide position 1258. The valine at codon 420 is replaced by isoleucine, an amino acid with highly 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. |