Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001224824 | SCV001397047 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2019-05-09 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 3185 of the PRKDC protein (p.Asn3185Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs531831112, ExAC 0.1%). This variant has not been reported in the literature in individuals with PRKDC-related disease. 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. 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. |