Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000217175 | SCV000271702 | uncertain significance | not specified | 2015-05-06 | criteria provided, single submitter | clinical testing | The p.Ser242Asn variant in DOLK has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. In summary, the clinical significance of the p.Ser242Asn var iant is uncertain. |
| Labcorp Genetics |
RCV000639758 | SCV000761339 | uncertain significance | DK1-congenital disorder of glycosylation | 2021-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 242 of the DOLK protein (p.Ser242Asn). 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: 228619). 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. |
| Fulgent Genetics, |
RCV000639758 | SCV002786144 | uncertain significance | DK1-congenital disorder of glycosylation | 2021-09-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003298280 | SCV003999103 | uncertain significance | Cardiovascular phenotype | 2023-04-03 | criteria provided, single submitter | clinical testing | The p.S242N variant (also known as c.725G>A), located in coding exon 1 of the DOLK gene, results from a G to A substitution at nucleotide position 725. The serine at codon 242 is replaced by asparagine, an amino acid with highly 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. |