Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_005249.5(FOXG1):c.685A>C (p.Ile229Leu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16621657

425040 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8f7a9d2e-ff03-406d-88b5-34d80f6d48d0

Approved on: 2022-02-18

Published on: 2022-06-30

HGVS expressions

NM_005249.5:c.685A>C

NM_005249.5(FOXG1):c.685A>C (p.Ile229Leu)

NC_000014.9:g.28767964A>C

CM000676.2:g.28767964A>C

NC_000014.8:g.29237170A>C

CM000676.1:g.29237170A>C

NC_000014.7:g.28306921A>C

NG_009367.1:g.5884A>C

ENST00000313071.7:c.685A>C

ENST00000313071.6:c.685A>C

NM_005249.4:c.685A>C

Likely Pathogenic

PM2_Supporting PM1 PM6 PP3

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Ile229Leu variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (PMID 18571142, 28661489) (PM1). The p.Ile229Leu variant in FOXG1 occurs in the de novo state (biological parentage unconfirmed) in an individual with intellectual disability and seizures (Genetic Services Laboratory, University of Chicago internal data)(PM6). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance (PP3). The p.Ile229Leu variant in FOXG1 is absent in gnomAD (PM2_supporting). In summary, the p.Ile229Leu variant in FOXG1 is classified as likely pathogenic for FOXG1 disorder based on the ACMG/AMP criteria (PM1, PM6, PP3, PM2_supporting).

PM2_Supporting

The p.Ile229Leu variant in FOXG1 is absent in gnomAD.

PM1

The p.Ile229Leu variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (Forkhead: aa 181-275; PMID 18571142, 28661489).

PM6

The p.Ile229Leu variant in FOXG1 occurs in the de novo state (biological parentage unconfirmed) in an individual with intellectual disability and seizures (Genetic Services Laboratory, University of Chicago internal data).

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance.

Curation History

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. If you have questions about the information contained on this website, please see a health care professional.