ClinVar Miner

Submissions for variant NM_133433.4(NIPBL):c.5366G>A (p.Arg1789Gln)

dbSNP: rs80358380
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000086381 SCV000193948 likely pathogenic Cornelia de Lange syndrome 1 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000086381 SCV000775591 uncertain significance Cornelia de Lange syndrome 1 2017-08-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1789 of the NIPBL protein (p.Arg1789Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant has not been reported in the literature in individuals with NIPBL-related disease. ClinVar contains an entry for this variant (Variation ID: 99932). This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute of Human Genetics, University of Leipzig Medical Center RCV000086381 SCV001440680 pathogenic Cornelia de Lange syndrome 1 2020-10-09 criteria provided, single submitter clinical testing This variant was identified as de novo (maternity and paternity confirmed).
Genome-Nilou Lab RCV000086381 SCV002054194 likely pathogenic Cornelia de Lange syndrome 1 2021-07-15 criteria provided, single submitter clinical testing
3billion RCV000086381 SCV002521357 likely pathogenic Cornelia de Lange syndrome 1 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.83; 3Cnet: 0.97). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with NIPBL related disorder (PMID: VCV000099932.5). Different missense changes at the same codon (p.Arg1789Gly, p.Arg1789Leu) have been reported to be associated with NIPBL related disorder (PMID: 15318302, 20583156). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV003236776 SCV003935665 pathogenic not provided 2023-06-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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