Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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). |
Gene |
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, |
RCV001781545 | SCV002026242 | pathogenic | Rett syndrome, congenital variant | 2018-01-20 | criteria provided, single submitter | clinical testing |