NM_005249.5(FOXG1):c.624C>A (p.Tyr208Ter) AND FOXG1 disorder

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Aug 25, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000550163.14

Allele description [Variation Report for NM_005249.5(FOXG1):c.624C>A (p.Tyr208Ter)]

NM_005249.5(FOXG1):c.624C>A (p.Tyr208Ter)

Gene:

FOXG1:forkhead box G1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_005249.5(FOXG1):c.624C>A (p.Tyr208Ter)

HGVS:

NC_000014.9:g.28767903C>A
NG_009367.1:g.5823C>A
NM_005249.5:c.624C>AMANE SELECT
NP_005240.3:p.Tyr208Ter
NC_000014.8:g.29237109C>A
NM_005249.3:c.624C>A
NM_005249.4:c.624C>A
p.Y208X

Protein change:

Y208*

Links:

dbSNP: rs267606826

Molecular consequence:

NM_005249.5:c.624C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: FOXG1 disorder
Synonyms:: RETT SYNDROME, CONGENITAL VARIANT
Identifiers:: MONDO: MONDO:0100040; MedGen: C3150705; Orphanet: 3095; OMIM: 613454

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000622146	Undiagnosed Diseases Network, NIH	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 5, 2016)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001399979	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 5, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28661489, 19578037, 28492532
SCV001427498	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	no assertion criteria provided	Pathogenic (Jan 1, 2019)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV006555471	Daryl Scott Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 25, 2025)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing
White	de novo	yes	1	not provided	not provided	not provided	no	clinical testing

Citations

PubMed

FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants.

Mitter D, Pringsheim M, Kaulisch M, Plümacher KS, Schröder S, Warthemann R, Abou Jamra R, Baethmann M, Bast T, Büttel HM, Cohen JS, Conover E, Courage C, Eger A, Fatemi A, Grebe TA, Hauser NS, Heinritz W, Helbig KL, Heruth M, Huhle D, Höft K, et al.

Genet Med. 2018 Jan;20(1):98-108. doi: 10.1038/gim.2017.75. Epub 2017 Jun 29.

PubMed [citation]

PMID:: 28661489

Novel FOXG1 mutations associated with the congenital variant of Rett syndrome.

Mencarelli MA, Spanhol-Rosseto A, Artuso R, Rondinella D, De Filippis R, Bahi-Buisson N, Nectoux J, Rubinsztajn R, Bienvenu T, Moncla A, Chabrol B, Villard L, Krumina Z, Armstrong J, Roche A, Pineda M, Gak E, Mari F, Ariani F, Renieri A.

J Med Genet. 2010 Jan;47(1):49-53. doi: 10.1136/jmg.2009.067884. Epub 2009 Jul 2.

PubMed [citation]

PMID:: 19578037

See all PubMed Citations (4)

Details of each submission

From Undiagnosed Diseases Network, NIH, SCV000622146.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	White	1	not provided	no	clinical testing	PubMed (1)

Description

This terminating amino acid change (p.Y208X) has been reported in at least one affected individual (PMID 19578037).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001399979.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This nonsense change has been observed in individual(s) with clinical features of Rett syndrome (PMID: 28661489, 19578037). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 453289). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the FOXG1 gene (p.Tyr208*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 282 amino acids of the FOXG1 protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille, SCV001427498.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Daryl Scott Lab, Baylor College of Medicine, SCV006555471.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

PVS1, PS2, PM2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 15, 2026

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