Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001364150 | SCV001560284 | uncertain significance | DK1-congenital disorder of glycosylation | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 380 of the DOLK protein (p.Arg380Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs775869216, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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 | RCV002322338 | SCV002606093 | uncertain significance | Cardiovascular phenotype | 2021-08-02 | criteria provided, single submitter | clinical testing | The p.R380C variant (also known as c.1138C>T), located in coding exon 1 of the DOLK gene, results from a C to T substitution at nucleotide position 1138. The arginine at codon 380 is replaced by cysteine, an amino acid with highly 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. |