NM_005249.5(FOXG1):c.356del (p.Ala119fs) AND Rett syndrome, congenital variant

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 17, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001953373.6

Allele description [Variation Report for NM_005249.5(FOXG1):c.356del (p.Ala119fs)]

NM_005249.5(FOXG1):c.356del (p.Ala119fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_005249.5(FOXG1):c.356del (p.Ala119fs)

HGVS:

NC_000014.9:g.28767635del
NG_009367.1:g.5555del
NM_005249.5:c.356delMANE SELECT
NP_005240.3:p.Ala119fs
NC_000014.8:g.29236841del

Protein change:

A119fs

Links:

dbSNP: rs2138660687

NCBI 1000 Genomes Browser:

rs2138660687

Molecular consequence:

NM_005249.5:c.356del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Rett syndrome, congenital variant
Identifiers:: MONDO: MONDO:0013270; MedGen: C3150705; Orphanet: 3095; OMIM: 613454

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LOC127405896 [Homo sapiens]
LOC127405896 [Homo sapiens]
Gene ID:127405896

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002220817	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 17, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24836831, 25356899, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002220817

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 17, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

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

Citations

PubMed

Epilepsy and outcome in FOXG1-related disorders.

Seltzer LE, Ma M, Ahmed S, Bertrand M, Dobyns WB, Wheless J, Paciorkowski AR.

Epilepsia. 2014 Aug;55(8):1292-300. doi: 10.1111/epi.12648. Epub 2014 May 16.

PubMed [citation]

PMID:: 24836831
PMCID:: PMC4265461

De novo mutations in moderate or severe intellectual disability.

Hamdan FF, Srour M, Capo-Chichi JM, Daoud H, Nassif C, Patry L, Massicotte C, Ambalavanan A, Spiegelman D, Diallo O, Henrion E, Dionne-Laporte A, Fougerat A, Pshezhetsky AV, Venkateswaran S, Rouleau GA, Michaud JL.

PLoS Genet. 2014 Oct;10(10):e1004772. doi: 10.1371/journal.pgen.1004772.

PubMed [citation]

PMID:: 25356899
PMCID:: PMC4214635

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002220817.3

#	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 variant disrupts the C-terminus of the FOXG1 protein. Other variant(s) that disrupt this region (p.Gly169Alafs*23) have been determined to be pathogenic (PMID: 24836831, 25356899). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with FOXG1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Ala119Valfs*73) in the FOXG1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 371 amino acid(s) 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

Last Updated: Sep 29, 2024

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