ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.471G>T (p.Lys157Asn)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel 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 (ga) RCV000081282 SCV000113190 uncertain significance not provided 2012-10-08 criteria provided, single submitter clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV000681508 SCV000808958 likely benign Intellectual disability 2017-01-01 criteria provided, single submitter clinical testing
Invitae 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.

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