Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002004216 | SCV002291579 | uncertain significance | Severe combined immunodeficiency due to DNA-PKcs deficiency | 2022-11-22 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRKDC protein function. ClinVar contains an entry for this variant (Variation ID: 1505745). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1700 of the PRKDC protein (p.Thr1700Ile). |
| Ambry Genetics | RCV004046157 | SCV003867786 | uncertain significance | not specified | 2022-12-27 | criteria provided, single submitter | clinical testing | The p.T1700I variant (also known as c.5099C>T), located in coding exon 39 of the PRKDC gene, results from a C to T substitution at nucleotide position 5099. The threonine at codon 1700 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |