Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV002810039 | SCV003761335 | pathogenic | Rett syndrome, congenital variant | 2023-01-25 | criteria provided, single submitter | curation | The heterozygous p.Lys213Ter variant in FOXG1 was identified by our study in one individual with Rett syndrome. Trio exome analysis showed this variant to be de novo. The p.Lys213Ter variant in FOXG1 has not been previously reported in individuals with Rett syndrome. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 181, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the FOXG1 gene is an established disease mechanism in Rett syndrome. In summary, this variant meets criteria to be classified as pathogenic for Rett syndrome. ACMG/AMP Criteria applied: PVS1, PS2_Moderate, PM2_Supporting (Richards 2015). |