Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002782056 | SCV003580648 | uncertain significance | Inborn genetic diseases | 2021-10-09 | criteria provided, single submitter | clinical testing | The c.680A>T (p.N227I) alteration is located in exon 1 (coding exon 1) of the FOXG1 gene. This alteration results from a A to T substitution at nucleotide position 680, causing the asparagine (N) at amino acid position 227 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003629239 | SCV004449632 | uncertain significance | Rett syndrome, congenital variant | 2023-03-28 | criteria provided, single submitter | clinical testing | This variant disrupts a region of the FOXG1 protein in which other variant(s) (p.Asn227) have been observed in individuals with FOXG1-related conditions (PMID: 19578037; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: 2248642). This variant has not been reported in the literature in individuals affected with FOXG1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 227 of the FOXG1 protein (p.Asn227Ile). |