Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000813534 | SCV000953897 | uncertain significance | DK1-congenital disorder of glycosylation | 2022-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 305 of the DOLK protein (p.Ser305Cys). This variant is present in population databases (rs766759178, gnomAD 0.003%). 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: 656997). 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 C15". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002372292 | SCV002686111 | uncertain significance | Cardiovascular phenotype | 2023-08-11 | criteria provided, single submitter | clinical testing | The p.S305C variant (also known as c.914C>G), located in coding exon 1 of the DOLK gene, results from a C to G substitution at nucleotide position 914. The serine at codon 305 is replaced by cysteine, an amino acid with dissimilar 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. |
Fulgent Genetics, |
RCV000813534 | SCV002777177 | uncertain significance | DK1-congenital disorder of glycosylation | 2022-03-18 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV004693352 | SCV005191114 | uncertain significance | not provided | criteria provided, single submitter | not provided |