Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002316066 | SCV000847528 | uncertain significance | Inborn genetic diseases | 2016-08-11 | criteria provided, single submitter | clinical testing | The p.T87P variant (also known as c.259A>C), located in coding exon 1 of the FOXG1 gene, results from an A to C substitution at nucleotide position 259. The threonine at codon 87 is replaced by proline, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 98 samples (196 alleles) with coverage at this position. This amino acid position is not conserved on limited sequence alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Labcorp Genetics |
RCV002533003 | SCV003346648 | uncertain significance | Rett syndrome, congenital variant | 2022-04-29 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FOXG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 588146). 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 not expected to disrupt FOXG1 protein function. 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 87 of the FOXG1 protein (p.Thr87Pro). |