ClinVar Miner

Submissions for variant NM_133433.4(NIPBL):c.6646T>C (p.Tyr2216His) (rs587784020)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146699 SCV000194014 uncertain significance Cornelia de Lange syndrome 1 2014-05-13 criteria provided, single submitter clinical testing
Invitae RCV000146699 SCV000815858 pathogenic Cornelia de Lange syndrome 1 2018-06-04 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 2216 of the NIPBL protein (p.Tyr2216His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Cornelia de Lange syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 159205). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Two other missense variants at this residue (p.Tyr2216Cys and p.Try2216Ser) in NIPBL have been determined to be clinically significant (PMID:24874887, 24635725). This suggests that variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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