ClinVar Miner

Submissions for variant NM_000168.6(GLI3):c.3155C>G (p.Pro1052Arg)

dbSNP: rs2128705843
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001658809 SCV001873935 uncertain significance not provided 2021-07-23 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002488446 SCV002789103 uncertain significance Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome; Polysyndactyly 4; Polydactyly, postaxial, type A1 2021-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003771819 SCV004570231 uncertain significance Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome 2023-03-18 criteria provided, single submitter clinical testing 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: 1254627). 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 GLI3 protein function. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1052 of the GLI3 protein (p.Pro1052Arg).
Ambry Genetics RCV004631729 SCV005123609 uncertain significance Inborn genetic diseases 2024-03-26 criteria provided, single submitter clinical testing The c.3155C>G (p.P1052R) alteration is located in exon 15 (coding exon 14) of the GLI3 gene. This alteration results from a C to G substitution at nucleotide position 3155, causing the proline (P) at amino acid position 1052 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.