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

dbSNP: rs267606826

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Undiagnosed Diseases Network, NIH	RCV000550163	SCV000622146	pathogenic	Rett syndrome, congenital variant	2016-08-05	criteria provided, single submitter	clinical testing	This terminating amino acid change (p.Y208X) has been reported in at least one affected individual (PMID 19578037).
Invitae	RCV000550163	SCV001399979	pathogenic	Rett syndrome, congenital variant	2020-03-05	criteria provided, single submitter	clinical testing	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.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003977	SCV001162003	pathogenic	Global developmental delay; Axial hypotonia; Stereotypic movement disorder; Strabismus; Abnormal optic nerve morphology		no assertion criteria provided	research
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV000550163	SCV001427498	pathogenic	Rett syndrome, congenital variant	2019-01-01	no assertion criteria provided	clinical testing