ClinVar Miner

Submissions for variant NM_133433.4(NIPBL):c.2584A>G (p.Lys862Glu) (rs1554017428)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000678375 SCV000804442 uncertain significance Cornelia de Lange syndrome 1 2017-08-28 criteria provided, single submitter provider interpretation This 5 year old male with global developmental delays, seizure disorder, and subcortical band heterotopia was found to carry a variant in the NIPBL gene. Inheritance is unknown as a paternal sample was unavailable. Clinical correlation is thought to be poor as the patient is non-dysmorphic and does not have limb defects. He is small for his age; he is below the 1st percentile for both height and weight. The variant is absent from population databases. It is a non-conservative substitution at a conserved position; in silico analysis is inconsistent in its predictions. Additionally, exome sequencing identified a pathogenic variant in PAFAH1B1.
GeneDx RCV000520338 SCV000618587 uncertain significance not provided 2017-06-22 criteria provided, single submitter clinical testing The K862E variant in the NIPBL gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The K862E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The K862E 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is inconsistent in its predictions as to whether or not the variant is damaging to to the protein structure/function. We interpret K862E as a variant of uncertain significance

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