Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004584203 | SCV005068290 | benign | FOXG1 disorder | 2024-04-18 | reviewed by expert panel | curation | The allele frequency of the p.Pro74Gln variant in FOXG1 is 0.018% in Admixed American sub population in gnomAD v4.0, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Pro74Gln variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). Computational analysis prediction tools suggest that the p.Pro74Gln variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Pro74Gln variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BS2, BP4, BS1). |
Gene |
RCV000187437 | SCV000241028 | likely benign | not specified | 2013-07-31 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Labcorp Genetics |
RCV002514002 | SCV002939690 | uncertain significance | Rett syndrome, congenital variant | 2023-08-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 74 of the FOXG1 protein (p.Pro74Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 205468). 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. |