ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.256dup (p.Gln86fs) (rs786205001)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187488 SCV000241082 pathogenic not provided 2018-05-23 criteria provided, single submitter clinical testing c.256dupC: p.Gln86ProfsX35 (Q86PfsX35) in exon 1 of the FOXG1 gene (NM_005249.3). The normal sequence with the base that is duplicated in braces is: GCCCCCC{C}AGAC. The c.256dupC pathogenic variant in the FOXG1 gene has been reported previously in a male patient with congenital Rett syndrome (Le Guen et al., 2011). The duplication causes a frameshift starting with codon Glutamine 86, changes this amino acid to a Proline residue and creates a premature Stop codon at position 35 of the new reading frame, denoted p.Gln86ProfsX35. This pathogenic mutation is predicted to cause loss of normal protein function through protein truncation as the last 404 amino acids are replaced with 34 incorrect amino acids. Therefore, the presence of c.256dupC is consistent with a diagnosis of congenital Rett syndrome. The variant is found in RETT-EPIV2-1 panel(s).
Invitae RCV000170074 SCV001203682 pathogenic Rett syndrome, congenital variant 2019-12-18 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the FOXG1 gene (p.Gln86Profs*35). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 404 amino acids of the FOXG1 protein. 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 been observed in individual(s) with congenital variant of Rett syndrome (PMID: 20734096). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 189613). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000187488 SCV001249820 pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing
RettBASE RCV000170074 SCV000222384 pathogenic Rett syndrome, congenital variant 2013-02-15 no assertion criteria provided curation

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