Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001811937 | SCV002048840 | uncertain significance | not provided | 2020-11-18 | criteria provided, single submitter | clinical testing | The DHTKD1 c.2629C>G, p.Pro877Ala variant (rs762777348), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the non-Finnish European population with an allele frequency of 0.0044% (5/113,766 alleles) in the Genome Aggregation Database. The proline at codon 877 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.371). Due to limited information, the clinical significance of this variant is uncertain at this time. |
| Labcorp Genetics |
RCV001869474 | SCV002184436 | uncertain significance | 2-aminoadipic 2-oxoadipic aciduria | 2023-01-26 | 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 DHTKD1 protein function. ClinVar contains an entry for this variant (Variation ID: 1330887). This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. This variant is present in population databases (rs762777348, gnomAD 0.004%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 877 of the DHTKD1 protein (p.Pro877Ala). |