Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002347678 | SCV002650190 | uncertain significance | Inborn genetic diseases | 2020-09-16 | criteria provided, single submitter | clinical testing | The p.D191N variant (also known as c.571G>A), located in coding exon 6 of the VRK1 gene, results from a G to A substitution at nucleotide position 571. The aspartic acid at codon 191 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and asparagine is the reference amino acid in other 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. |
Labcorp Genetics |
RCV003096852 | SCV003247364 | uncertain significance | Pontocerebellar hypoplasia type 1A | 2022-08-01 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 191 of the VRK1 protein (p.Asp191Asn). This variant is present in population databases (rs138470389, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with VRK1-related conditions. 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. |