Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188746 | SCV000242370 | uncertain significance | not provided | 2014-11-18 | criteria provided, single submitter | clinical testing | p.Ala506Thr (GCT>ACT): c.1516 G>A in exon 7 of the PRICKLE1 gene (NM_153026.2). The A506T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A506T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved through mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s). |
Invitae | RCV001857644 | SCV002255008 | uncertain significance | Epilepsy, progressive myoclonic, 1B | 2021-09-05 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 206669). This variant has not been reported in the literature in individuals affected with PRICKLE1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 506 of the PRICKLE1 protein (p.Ala506Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. |