Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001209746 | SCV001381196 | uncertain significance | DK1-congenital disorder of glycosylation | 2022-04-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 428 of the DOLK protein (p.Gln428Pro). This variant is present in population databases (rs189623590, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 940209). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV002379795 | SCV002695740 | uncertain significance | Cardiovascular phenotype | 2022-06-14 | criteria provided, single submitter | clinical testing | The p.Q428P variant (also known as c.1283A>C), located in coding exon 1 of the DOLK gene, results from an A to C substitution at nucleotide position 1283. The glutamine at codon 428 is replaced by proline, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |