Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000689083 | SCV000816721 | uncertain significance | Epilepsy, progressive myoclonic, 1B | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 471 of the PRICKLE1 protein (p.Met471Thr). This variant is present in population databases (rs777597253, gnomAD 0.09%). 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: 568656). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRICKLE1 protein function with a negative predictive value of 80%. 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 | RCV002388220 | SCV002699685 | uncertain significance | Inborn genetic diseases | 2020-05-29 | criteria provided, single submitter | clinical testing | The p.M471T variant (also known as c.1412T>C), located in coding exon 6 of the PRICKLE1 gene, results from a T to C substitution at nucleotide position 1412. The methionine at codon 471 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |