ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.670G>A (p.Gly224Ser)

dbSNP: rs727503935
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV002260625 SCV002540696 likely pathogenic FOXG1 disorder 2022-02-18 reviewed by expert panel curation The p.Gly224Ser variant in FOXG1 is located in the well-characterized Forkhead functional domain (PMID 18571142, 28661489)(PM1). The p.Gly224Ser variant in FOXG1 occurs in the de novo state (biological parentage unconfirmed) in an individual with gross motor delay and infantile spasms (GeneDx internal database)(PM6). The p.Gly224Ser variant in FOXG1 is absent in gnomAD (PM2_supporting). The p.Gly224Ser variant has been observed in 2 individuals with neurodevelopmental disease (GeneDx internal database, University of Chicago internal database)(PS4_supporting). In summary, the p.Gly224Ser variant in FOXG1 is classified as likely pathogenic based on the ACMG/AMP criteria (PM1, PM6, PM2_supporting, PS4_supporting).
Eurofins NTD LLC (GA) RCV000153265 SCV000202741 likely pathogenic not provided 2014-04-09 criteria provided, single submitter clinical testing
GeneDx RCV000153265 SCV000492334 likely pathogenic not provided 2016-12-13 criteria provided, single submitter clinical testing A G224S variant that is likely pathogenic has been identified in the FOXG1 gene. The G224S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G224S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G224S 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 across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, the G224S variant occurs within the forkhead binding domain where all previously reported missense variants in FOXG1 have been identified and multiple missense variants in nearby residues have been reported in Human Gene Mutation Database in association with FOXG1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Genetic Services Laboratory,University of Chicago RCV000500932 SCV000594858 likely pathogenic Rett syndrome, congenital variant 2016-03-25 criteria provided, single submitter clinical testing
Invitae RCV000500932 SCV000650056 uncertain significance Rett syndrome, congenital variant 2021-08-26 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000500932 SCV000700153 likely pathogenic Rett syndrome, congenital variant 2017-03-30 criteria provided, single submitter clinical testing

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.