ClinVar Miner

Submissions for variant NM_017890.4(VPS13B):c.11825_11827dup (p.Asp3942dup) (rs386834068)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000081876 SCV000113811 uncertain significance not provided 2013-10-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000717810 SCV000848670 uncertain significance History of neurodevelopmental disorder 2018-12-07 criteria provided, single submitter clinical testing The c.11825_11827dupATG variant (also known as p.D3942dup), located in coding exon 61 of the VPS13B gene, results from an in-frame duplication of ATG at nucleotide positions 11825 to 11827. This results in the duplication of an aspartate residue between codons 3942 and 3943. This duplication (reported as p.D3942_G3943insD) was detected in compound heterozygous state with a gross deletion encompassing exons 1 to 17 of VPS13B and exon 4 of ORS2 in a patient with developmental delay and cardiac defect (Rivera-Brugués N et al. J. Med. Genet., 2011 Feb;48:136-40). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by PROVEAN in silico analysis (Choi Y et al., PLoS ONE 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000050055 SCV000899088 uncertain significance Cohen syndrome 2018-02-02 criteria provided, single submitter clinical testing VPS13B NM_017890.4 exon 62 p.Asp3942_dup (c.11825_11827dupATG): This variant has been reported in the literature as a compound heterozygote (in trans with a multi-exon deletion of this gene) in 1 individual with a diagnosis of Cohen syndrome (Rivera-Brugues 2011 PMID:20921020, gene identified as alternate name COH1). However, this variant is present in 0.4% (100/24024) of African alleles in the Genome Aggregation Database ( This variant is present in ClinVar (Variation ID:56642). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents a duplication of 1 amino acid at position 3942 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV000050055 SCV000963968 likely benign Cohen syndrome 2020-12-07 criteria provided, single submitter clinical testing
Mendelics RCV000050055 SCV001137692 uncertain significance Cohen syndrome 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV000081876 SCV001819828 likely benign not provided 2021-02-26 criteria provided, single submitter clinical testing In-frame insertion of one amino acid in a non-repeat region; Reported previously using alternate nomenclature (c.1827_11828insATG) in an individual with developmental delay, cardiac defects, and dysmorphic features who harbored a partial gene deletion on the opposite allele (in trans) (Rivera-Brugues et al., 2011); This variant is associated with the following publications: (PMID: 20921020)
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050055 SCV000082464 probable-pathogenic Cohen syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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