ClinVar Miner

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

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187475 SCV000241068 pathogenic not provided 2017-11-25 criteria provided, single submitter clinical testing c.256delC: p.Gln86ArgfsX106 (Q86RfsX106) in exon 1 of the FOXG1 gene (NM_005249.3). The normal sequence with the base that is deleted in braces is: GCCCCCC[C]AGAC. The c.256delC pathogenic variant in the FOXG1 gene has been reported previously in a male with clinical features of FOXG1 syndrome and Rett syndrome (Allou et al., 2012). The deletion causes a frameshift starting with codon Glutamine 86, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 106 of the new reading frame, denoted p.Gln86ArgfsX106. This variant is predicted to cause loss of normal protein function through protein truncation.
Genetic Services Laboratory,University of Chicago RCV000170073 SCV000247413 pathogenic Rett syndrome, congenital variant 2014-10-30 criteria provided, single submitter clinical testing
Invitae RCV000170073 SCV000676980 pathogenic Rett syndrome, congenital variant 2019-12-11 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the FOXG1 gene (p.Gln86Argfs*106). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 404 amino acids (~82%) of the FOXG1 protein. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported to be de novo in individuals affected with Rett-like syndrome (PMID: 22739344) and FOXG1 syndrome with hyperkinetic movement disorder (PMID: 26344814). ClinVar contains an entry for this variant (Variation ID: 189612). For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company RCV000170073 SCV001426430 pathogenic Rett syndrome, congenital variant criteria provided, single submitter clinical testing
RettBASE RCV000170073 SCV000222383 pathogenic Rett syndrome, congenital variant 2013-02-15 no assertion criteria provided curation

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