Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001068790 | SCV001233922 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2020-02-22 | criteria provided, single submitter | clinical testing | 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. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PRKDC-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces glutamic acid with glutamine at codon 41 of the PRKDC protein (p.Glu41Gln). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and glutamine. |
| Ambry Genetics | RCV002355095 | SCV002655210 | uncertain significance | Inborn genetic diseases | 2022-03-09 | criteria provided, single submitter | clinical testing | The p.E41Q variant (also known as c.121G>C), located in coding exon 1 of the PRKDC gene, results from a G to C substitution at nucleotide position 121. The glutamic acid at codon 41 is replaced by glutamine, 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. |