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.565C>G (p.Leu189Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA389475372

547390 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e62185d2-30c7-40d4-9a85-7f2c329113b1

Approved on: 2023-04-14

Published on: 2023-06-16

HGVS expressions

NM_005249.5:c.565C>G

NM_005249.5(FOXG1):c.565C>G (p.Leu189Val)

NC_000014.9:g.28767844C>G

CM000676.2:g.28767844C>G

NC_000014.8:g.29237050C>G

CM000676.1:g.29237050C>G

NC_000014.7:g.28306801C>G

NG_009367.1:g.5764C>G

ENST00000313071.7:c.565C>G

ENST00000313071.6:c.565C>G

NM_005249.4:c.565C>G

Likely Pathogenic

PP3 PM5 PM1 PM2_Supporting

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.Leu189Val variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (PM1). The p.Leu189Val variant in FOXG1 is absent from gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). A pathogenic missense variant (p.Leu189Phe) has been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 28661489, GeneDx internal database)(PM5). In summary, the p.Leu189Val variant in FOXG1 is classified as likely pathogenic for a FOXG1-related disorder based on the ACMG/AMP criteria (PM1, PM2_supporting, PP3, PM5).

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).

PM5

A pathogenic missense variant (p.Leu189Phe) has been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 28661489, GeneDx internal database)

PM1

The p.Leu189Val variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (PM1).

PM2_Supporting

The p.Leu189Val variant in FOXG1 is absent from gnomAD (PM2_supporting).

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.