ClinVar Miner

Submissions for variant NM_000168.6(GLI3):c.1613G>A (p.Arg538Lys)

dbSNP: rs2128712790
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001761025 SCV001999819 uncertain significance not provided 2022-10-13 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV005225477 SCV005868933 uncertain significance Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome 2024-05-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 538 of the GLI3 protein (p.Arg538Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GLI3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1310855). 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 expected to disrupt GLI3 protein function with a positive 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.