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.681C>G (p.Asn227Lys)

CA199447

189623 (ClinVar)

Gene: FOXG1

Condition: FOXG1 disorder

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 0f00526b-3e4f-4459-ba6f-d15f995ecbb4

Approved on: 2023-04-14

Published on: 2023-06-16

HGVS expressions

NM_005249.5:c.681C>G

NM_005249.5(FOXG1):c.681C>G (p.Asn227Lys)

NC_000014.9:g.28767960C>G

CM000676.2:g.28767960C>G

NC_000014.8:g.29237166C>G

CM000676.1:g.29237166C>G

NC_000014.7:g.28306917C>G

NG_009367.1:g.5880C>G

ENST00000313071.7:c.681C>G

ENST00000313071.6:c.681C>G

NM_005249.4:c.681C>G

Uncertain Significance

PP3 PM2_Supporting PM1

PP4

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.Asn227Lys variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (PM1). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Asn227Lys variant in FOXG1 is absent from gnomAD (PM2_supporting). The p.Asn227Lys variant was observed in an individual with microcephaly, rocking movements, absent speech, epilepsy, bruxism, severe scoliosis, and who is non-ambulatory. However, this individual's parents were not available for segregation analysis and this individual was evaluated once at the age of 13 years old (PMID 19578037) (PP4_not met). In summary, the p.Asn227Lys variant in FOXG1 is classified as a variant of uncertain significance based on the ACMG/AMP criteria (PM1, PP3, PM2_supporting).

PP3

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

PM2_Supporting

The p.Asn227Lys variant in FOXG1 is absent from gnomAD

PM1

The p.Asn227Lys variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene.

PP4

Observed in an individual with microcephaly, rocking movements, absent speech, epilepsy, bruxism, severe scoliosis, and who is non-ambulatory. This individual's parents were not available and this individual was evaluated once at the age of 13 years old (PMID 19578037).

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