Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002281056 | SCV002569944 | likely benign | FOXG1 disorder | 2022-09-01 | reviewed by expert panel | curation | The p.Lys157Asn variant in FOXG1 is present in 2 individuals in gnomAD (0.001%) (not sufficient to meet BS1 criteria). The p.Lys157Asn variant is observed in at least 2 unaffected individuals (internal database) (BS2). Computational analysis prediction tools suggest that the p.Lys157Asn variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Lys157Asn variant in FOXG1 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP4). |
Eurofins Ntd Llc |
RCV000081282 | SCV000113190 | uncertain significance | not provided | 2012-10-08 | criteria provided, single submitter | clinical testing | |
Centre de Biologie Pathologie Génétique, |
RCV000681508 | SCV000808958 | likely benign | Intellectual disability | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000822082 | SCV000962868 | uncertain significance | Rett syndrome, congenital variant | 2018-08-29 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 157 of the FOXG1 protein (p.Lys157Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with FOXG1-related disease. ClinVar contains an entry for this variant (Variation ID: 95269). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |