Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000688325 | SCV000815931 | uncertain significance | DK1-congenital disorder of glycosylation | 2022-11-15 | 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 expected to disrupt DOLK protein function. ClinVar contains an entry for this variant (Variation ID: 568082). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 98 of the DOLK protein (p.Arg98Trp). |
| Ambry Genetics | RCV002440433 | SCV002748783 | uncertain significance | Cardiovascular phenotype | 2021-09-10 | criteria provided, single submitter | clinical testing | The p.R98W variant (also known as c.292C>T), located in coding exon 1 of the DOLK gene, results from a C to T substitution at nucleotide position 292. The arginine at codon 98 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV000688325 | SCV002779135 | uncertain significance | DK1-congenital disorder of glycosylation | 2021-09-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004719946 | SCV005325605 | uncertain significance | not provided | 2024-09-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |