Submissions for variant NM_005249.5(FOXG1):c.214C>T (p.Gln72Ter)

dbSNP: rs1555321237

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000576162	SCV000676978	pathogenic	Rett syndrome, congenital variant	2017-05-26	criteria provided, single submitter	clinical testing	This sequence change results in a premature translational stop signal in the FOXG1 gene (p.Gln72*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 418 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 not been reported in the literature in individuals with a FOXG1-related disease. 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. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV001093029	SCV001249819	pathogenic	not provided	2021-11-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000576162	SCV002026218	pathogenic	Rett syndrome, congenital variant	2018-01-20	criteria provided, single submitter	clinical testing
Solve-RD Consortium	RCV000576162	SCV005091322	likely pathogenic	Rett syndrome, congenital variant	2022-06-01	no assertion criteria provided	provider interpretation	Variant confirmed as disease-causing by referring clinical team