ClinVar Miner

Submissions for variant NM_133433.4(NIPBL):c.7301A>G (p.Asn2434Ser) (rs80358384)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412771 SCV000491554 likely pathogenic not provided 2016-08-31 criteria provided, single submitter clinical testing The N2434S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It has been reported reported as likely pathogenic in ClinVar by a different clinical laboratory, but additional evidence is not available (ClinVar SCV000194037.1; Landrum et al., 2015). The N2434S variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, 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. Missense variants in nearby residues (Y2430C, D2433N/G, A2436T) have been reported in the Human Gene Mutation Database in association with Cornelia de Lange syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Genetic Services Laboratory, University of Chicago RCV000086389 SCV000194037 likely pathogenic Cornelia de Lange syndrome 1 2013-02-08 criteria provided, single submitter clinical testing

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