Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000805203 | SCV000945151 | uncertain significance | Epilepsy, progressive myoclonic, 1B | 2022-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 149 of the PRICKLE1 protein (p.Val149Met). This variant is present in population databases (rs751791144, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with PRICKLE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 650112). 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 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 | RCV002332643 | SCV002638835 | uncertain significance | Inborn genetic diseases | 2017-07-06 | criteria provided, single submitter | clinical testing | The p.V149M variant (also known as c.445G>A), located in coding exon 4 of the PRICKLE1 gene, results from a G to A substitution at nucleotide position 445. The valine at codon 149 is replaced by methionine, an amino acid with highly similar 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. |