ClinVar Miner

Submissions for variant NM_000814.6(GABRB3):c.758C>T (p.Pro253Leu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486184 SCV000573312 likely pathogenic not provided 2017-03-03 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the GABRB3 gene. The P253L variant has been reported previously as a de novo variant in the mosaic state in an individual with seizures, epileptic encephalopathy, severe intellectual disability and autistic features (Moller et al., 2017). The P253L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P253L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (Q249K, L256Q) have been reported in the Human Gene Mutation Database in association with GABRB3-related disorders (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV001004658 SCV001164106 likely pathogenic Epileptic encephalopathy, early infantile, 43 2015-12-14 criteria provided, single submitter clinical testing

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