Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001307726 | SCV001497149 | uncertain significance | DK1-congenital disorder of glycosylation | 2022-05-30 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1010141). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. This variant is present in population databases (rs780799327, gnomAD 0.007%). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 473 of the DOLK protein (p.Phe473Leu). |
| Ambry Genetics | RCV002393730 | SCV002698554 | uncertain significance | Cardiovascular phenotype | 2022-07-06 | criteria provided, single submitter | clinical testing | The p.F473L variant (also known as c.1419T>G), located in coding exon 1 of the DOLK gene, results from a T to G substitution at nucleotide position 1419. The phenylalanine at codon 473 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |