ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.460del (p.Glu154fs) (rs398124204)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000209851 SCV000265612 pathogenic Rett syndrome, congenital variant 2016-02-11 criteria provided, single submitter research
GeneDx RCV000414502 SCV000490904 pathogenic not provided 2015-09-16 criteria provided, single submitter clinical testing The c.460delG variant in the FOXG1 gene causes a frameshift starting with codon Glutamic acid 154,changes this amino acid to an Arginine residue and creates a premature Stop codon at position 38 of thenew reading frame, denoted p.E154RfsX38. Thisvariant is predicted to cause loss of normal proteinfunction through protein truncation, as the last 336 amino acid residues are replaced with 37 incorrectamino acid residues. Although this variant has not been previously reported to our knowledge, we interpret is as pathogenic.
Invitae RCV000209851 SCV000952234 pathogenic Rett syndrome, congenital variant 2019-07-23 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the FOXG1 gene (p.Glu154Argfs*38). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 256 amino acids 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 not been reported in the literature in individuals with FOXG1-related disease. ClinVar contains an entry for this variant (Variation ID: 372563). A different truncation (p.Gly169Alafs*23) that lies downstream of this variant has been determined to be pathogenic (PMID: 24836831, 25356899). This suggests that deletion of this region of the FOXG1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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