Submissions for variant NM_005249.5(FOXG1):c.824G>C (p.Arg275Pro)

dbSNP: rs1555321361

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000505226	SCV002201869	uncertain significance	Rett syndrome, congenital variant	2022-02-08	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 275 of the FOXG1 protein (p.Arg275Pro). This variant has not been reported in the literature in individuals affected with FOXG1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FOXG1 protein function. ClinVar contains an entry for this variant (Variation ID: 438293).
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000505226	SCV000599262	likely pathogenic	Rett syndrome, congenital variant	2016-03-16	no assertion criteria provided	clinical testing