Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493967 | SCV000582508 | uncertain significance | not provided | 2017-05-09 | criteria provided, single submitter | clinical testing | The A91V variant in the DHTKD1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A91V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A91V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A91V as a variant of uncertain significance. |
Labcorp Genetics |
RCV001865548 | SCV002206942 | uncertain significance | 2-aminoadipic 2-oxoadipic aciduria | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 91 of the DHTKD1 protein (p.Ala91Val). This variant is not present in population databases (gnomAD no frequency). 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: 429842). 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. 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. |