ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.561C>A (p.Asn187Lys)

dbSNP: rs796052462
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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 RCV001507060 SCV001712028 pathogenic FOXG1 disorder 2021-03-25 reviewed by expert panel curation The p.Asn187Lys variant in FOXG1 has been reported as a de novo occurrence (biological parenthood confirmed) in at least 2 individuals with FOXG1 disorder (PMID 26795593, 28661489) (PS2_very strong). The p.Asn187Lys variant in FOXG1 has been observed in at least 5 other individuals with FOXG1 disorder (PMID 26795593, 25356970, 28661489) (PS4). This variant occurs in the well-characterized Forkhead functional domain of the FOXG1 (PM1). The p.Asn187Lys variant in FOXG1 is absent from gnomAD (PM2_supporting). In summary, the p.Asn187Lys variant in FOXG1 is classified as Pathogenic for FOXG1 disorder based on the ACMG/AMP criteria (PS2_very strong, PS4, PM1, PM2_supporting).
GeneDx RCV000187456 SCV000241049 pathogenic not provided 2016-06-23 criteria provided, single submitter clinical testing The Asn187Lys missense change has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Asn187Lys in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as an uncharged Asparagine residue is replaced by a positively charged Lysine residue. It alters a conserved position in the forkhead binding domain where all previously reported missense variant in FOXG1 have been identified. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Asn187Lys is a disease-causing variant or a rare benign variant.
Ambry Genetics RCV000190704 SCV000244145 pathogenic Inborn genetic diseases 2013-09-12 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001781545 SCV002026242 pathogenic Rett syndrome, congenital variant 2018-01-20 criteria provided, single submitter clinical testing

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