ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.460dup (p.Glu154fs) (rs398124204)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000081281 SCV000241072 pathogenic not provided 2018-12-31 criteria provided, single submitter clinical testing The c.460dupG variant in the FOXG1 gene has been reported previously in multiple individuals with FOXG1-related disorders (Bahi-Buisson et al., 2010; Seltzer et al., 2014; RettSyndrome.org Variation Database). This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.460dupG variant causes a frameshift starting with codon Glutamic acid 154, changes this amino acid to a Glycine residue, and creates a premature Stop codon at position 301 of the new reading frame, denoted p.Glu154GlyfsX301. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 336 amino acids are lost and replaced with 300 incorrect ones.
Genetic Services Laboratory,University of Chicago RCV000170075 SCV000247416 pathogenic Rett syndrome, congenital variant 2014-10-16 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000081281 SCV000331515 pathogenic not provided 2015-08-27 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000170075 SCV000484841 pathogenic Rett syndrome, congenital variant 2016-11-03 criteria provided, single submitter clinical testing
Invitae RCV000170075 SCV000824009 pathogenic Rett syndrome, congenital variant 2019-08-05 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the FOXG1 gene (p.Glu154Glyfs*301). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 336 amino acids of the FOXG1 protein. 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 variant has been observed to be de novo as well as inherited in individuals and families affected with FOXG1-related disorders (PMID: 26344814, 21441262, 19806373, 28851325, 24836831, 28661489). ClinVar contains an entry for this variant (Variation ID: 95268). This variant is also known as c.454dupG in the literature. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000715099 SCV000845925 pathogenic History of neurodevelopmental disorder 2016-08-08 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Undiagnosed Diseases Network,NIH RCV000170075 SCV001245596 pathogenic Rett syndrome, congenital variant 2019-03-18 criteria provided, single submitter clinical testing RV is pathogenic and not maternally transmitted, Dad unavailable; patient is good phenotypic match for condition
CeGaT Praxis fuer Humangenetik Tuebingen RCV000081281 SCV001249822 pathogenic not provided 2018-04-01 criteria provided, single submitter clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000170075 SCV001335519 pathogenic Rett syndrome, congenital variant criteria provided, single submitter clinical testing
RettBASE RCV000170075 SCV000222386 pathogenic Rett syndrome, congenital variant 2012-05-18 no assertion criteria provided curation
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000170075 SCV001364270 pathogenic Rett syndrome, congenital variant 2020-02-19 no assertion criteria provided clinical testing
Service de Génétique Moléculaire,Hôpital Robert Debré RCV000170075 SCV001432381 pathogenic Rett syndrome, congenital variant no assertion criteria provided clinical testing

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