Submissions for variant NM_005249.5(FOXG1):c.703C>T (p.Leu235Phe)

dbSNP: rs1566445489

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000706347	SCV000835390	likely pathogenic	Rett syndrome, congenital variant	2020-09-18	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with phenylalanine at codon 235 of the FOXG1 protein (p.Leu235Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with gait abnormalities, developmental delay, and hypotonia (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München	RCV000706347	SCV001430114	likely pathogenic	Rett syndrome, congenital variant	2020-03-13	criteria provided, single submitter	clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV001374989	SCV001572277	pathogenic	Neurodevelopmental disorder	2018-09-20	criteria provided, single submitter	clinical testing