ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.430G>A (p.Glu144Lys) (rs797045583)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192946 SCV000247415 uncertain significance not specified 2015-07-21 criteria provided, single submitter clinical testing
GeneDx RCV000766682 SCV000529020 uncertain significance not provided 2017-01-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FOXG1 gene. The E144K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E144K variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E144K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position where amino acids with similar properties to Glutamic acid are tolerated across species and it does not occur within the forkhead binding domain where all previously reported missense variants in FOXG1 have been identified. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Mendelics RCV000989198 SCV001139426 uncertain significance Rett syndrome, congenital variant 2019-05-28 criteria provided, single submitter clinical testing

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