ClinVar Miner

Submissions for variant NM_201525.4(ADGRG1):c.1490T>C (p.Leu497Pro)

gnomAD frequency: 0.00001  dbSNP: rs587783654
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146041 SCV000193196 likely pathogenic Bilateral frontoparietal polymicrogyria 2013-02-08 criteria provided, single submitter clinical testing
GeneDx 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.

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