ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.506dup (p.Lys170fs)

dbSNP: rs1452295073
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599217 SCV000709925 pathogenic not provided 2018-02-02 criteria provided, single submitter clinical testing The c.506dupG variant in the FOXG1 gene has been reported previously as presumed de novo in an individual with severe developmental delay, intellectual disability, acquired microcephaly, trigonocephaly, abnormal brain MRI, and infantile spasms (De Bruyn et al., 2014). The c.506dupG variant causes a frameshift starting with codon Lysine 170, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 285 of the new reading frame, denoted p.Lys170GlnfsX285. This variant is predicted to cause loss of normal protein function through protein truncation. The c.506dupG variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.506dupG as a pathogenic variant.
Institute of Human Genetics, University of Leipzig Medical Center RCV001783103 SCV002026234 pathogenic Rett syndrome, congenital variant 2018-01-20 criteria provided, single submitter clinical testing
Centre for Population Genomics, CPG RCV004559249 SCV005046865 pathogenic FOXG1 disorder 2024-05-24 criteria provided, single submitter curation This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as Pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant has been identified as a de novo occurrence in an individual with FOXG1 disorder without confirmation of paternity and maternity (PM6, PMID: 24388699). This variant is absent from gnomAD (PM2_Supporting).

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.