Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002707453 | SCV003548824 | uncertain significance | Inborn genetic diseases | 2020-11-20 | criteria provided, single submitter | clinical testing | The c.1696G>A (p.G566R) alteration is located in exon 9 (coding exon 9) of the DHTKD1 gene. This alteration results from a G to A substitution at nucleotide position 1696, causing the glycine (G) at amino acid position 566 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003528432 | SCV004271565 | uncertain significance | 2-aminoadipic 2-oxoadipic aciduria | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 566 of the DHTKD1 protein (p.Gly566Arg). 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 variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2228127). 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 DHTKD1 protein function with a negative predictive value of 80%. 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. |