Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523766 | SCV000620395 | uncertain significance | not provided | 2017-08-24 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DOLK gene. The M237T variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M237T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position where only amino acids with similar properties to methionine (M) are tolerated across species. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
Labcorp Genetics |
RCV001370425 | SCV001566907 | uncertain significance | DK1-congenital disorder of glycosylation | 2024-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 237 of the DOLK protein (p.Met237Thr). This variant is not present in population databases (gnomAD no frequency). 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: 451666). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DOLK 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. |
Ambry Genetics | RCV002367743 | SCV002666883 | uncertain significance | Cardiovascular phenotype | 2021-12-16 | criteria provided, single submitter | clinical testing | The p.M237T variant (also known as c.710T>C), located in coding exon 1 of the DOLK gene, results from a T to C substitution at nucleotide position 710. The methionine at codon 237 is replaced by threonine, an amino acid with 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. |
Fulgent Genetics, |
RCV001370425 | SCV002782382 | uncertain significance | DK1-congenital disorder of glycosylation | 2021-08-13 | criteria provided, single submitter | clinical testing |