Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000146041 | SCV000193196 | likely pathogenic | Bilateral frontoparietal polymicrogyria | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000255359 | SCV000322516 | likely pathogenic | not provided | 2016-01-20 | criteria provided, single submitter | clinical testing | The L503P variant in the GPR56 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L503P variant was not observed in approximately 6500 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 L503P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. The L503P variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
New York Genome Center | RCV002227448 | SCV002506760 | likely pathogenic | Bilateral frontoparietal polymicrogyria; Polymicrogyria, bilateral perisylvian, autosomal recessive | 2021-06-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000255359 | SCV003482369 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 503 of the ADGRG1 protein (p.Leu503Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ADGRG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 158620). 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 disruptive. 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. |