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]

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Variant: NM_005249.5(FOXG1):c.573G>A (p.Met191Ile)

CA389475390

452682 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8fe613d8-a9ab-40ae-9680-9983e488b1d3

Approved on: 2023-04-14

Published on: 2023-06-16

HGVS expressions

NM_005249.5:c.573G>A

NM_005249.5(FOXG1):c.573G>A (p.Met191Ile)

NC_000014.9:g.28767852G>A

CM000676.2:g.28767852G>A

NC_000014.8:g.29237058G>A

CM000676.1:g.29237058G>A

NC_000014.7:g.28306809G>A

NG_009367.1:g.5772G>A

ENST00000313071.7:c.573G>A

ENST00000313071.6:c.573G>A

NM_005249.4:c.573G>A

Likely Pathogenic

PP3 PM2_Supporting PM5 PM1

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.Met191Ile variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (PM1). The p.Met191Ile 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.Met191Arg) has been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 26364767, 26993267) (PM5). In summary, the p.Met191Ile 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)

PM2_Supporting

The p.Met191Ile variant in FOXG1 is absent from gnomAD (PM2).

PM5

A pathogenic missense variant (p.Met191Arg) has been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 26364767, 26993267)

PM1

The p.Met191Ile variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (PM1).

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