NM_005249.5(FOXG1):c.177_186dup (p.Pro63fs) AND Rett syndrome, congenital variant

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 24, 2017
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:: RCV000648316.8

Allele description [Variation Report for NM_005249.5(FOXG1):c.177_186dup (p.Pro63fs)]

NM_005249.5(FOXG1):c.177_186dup (p.Pro63fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_005249.5(FOXG1):c.177_186dup (p.Pro63fs)

HGVS:

NC_000014.9:g.28767456_28767465dup
NG_009367.1:g.5376_5385dup
NM_005249.5:c.177_186dupMANE SELECT
NP_005240.3:p.Pro63fs
NC_000014.8:g.29236655_29236656insCCCGCCGCCG
NC_000014.8:g.29236662_29236671dup
NM_005249.3:c.177_186dupGCCGCCCGCC
NM_005249.4(FOXG1):c.177_186dup
NM_005249.4:c.177_186dupGCCGCCCGCC
p.Pro63Alafs

Protein change:

P63fs

Links:

dbSNP: rs1555321206

NCBI 1000 Genomes Browser:

rs1555321206

Molecular consequence:

NM_005249.5:c.177_186dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000770130	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 24, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24836831, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000770130

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 24, 2017)

germline

clinical testing

PubMed (2)
[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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000770130.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Multiple truncations downstream of this variant have been determined to be pathogenic (PMID: 24836831). This suggests that deletion of this region of the FOXG1 protein is causative of disease. This variant has not been reported in the literature in individuals with FOXG1-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change results in a premature translational stop signal in the FOXG1 gene (p.Pro63Alafs*61). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 427 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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine