Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000696386 | SCV000824946 | uncertain significance | Congenital pontocerebellar hypoplasia type 1 | 2018-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with phenylalanine at codon 3 of the VRK1 protein (p.Arg3Phe). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VRK1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | RCV002360772 | SCV002666625 | uncertain significance | Inborn genetic diseases | 2021-03-19 | criteria provided, single submitter | clinical testing | The c.7_8delCGinsTT variant (also known as p.R3F), located in coding exon 1 of the VRK1 gene, results from an in-frame deletion of CG and insertion of TT at nucleotide positions 7 to 8. This results in the substitution of the arginine residue for a phenylalanine residue at codon 3, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Mayo Clinic Laboratories, |
RCV004792396 | SCV005409811 | uncertain significance | not provided | 2023-06-28 | criteria provided, single submitter | clinical testing |