Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000704997 | SCV000833974 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2018-06-20 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with histidine at codon 1192 of the PRKDC protein (p.Tyr1192His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs370182783, ExAC 0.001%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PRKDC-related disease. |
| Ambry Genetics | RCV004026679 | SCV002613267 | uncertain significance | not specified | 2022-10-19 | criteria provided, single submitter | clinical testing | The p.Y1192H variant (also known as c.3574T>C), located in coding exon 30 of the PRKDC gene, results from a T to C substitution at nucleotide position 3574. The tyrosine at codon 1192 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |