ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.11885C>G (p.Pro3962Arg)

gnomAD frequency: 0.00009  dbSNP: rs531619892
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768134 SCV000899089 uncertain significance Cohen syndrome 2021-03-30 criteria provided, single submitter clinical testing VPS13B NM_017890.4 exon62 p.Pro3987Arg (c.11960C>G): This variant has been reported in the literature in 1 individual with autism spectrum disorder (Koshimizu 2013 PMID:24066114). This variant is present in 0.004% (1/24968) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/8-100887785-C-G). Evolutionary conservation for this variant is unclear; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000768134 SCV000931369 uncertain significance Cohen syndrome 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 3987 of the VPS13B protein (p.Pro3987Arg). This variant is present in population databases (rs531619892, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 626049). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt VPS13B protein function. 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.
Genetic Services Laboratory, University of Chicago RCV001816824 SCV002071438 uncertain significance not specified 2018-02-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV000768134 SCV002085002 uncertain significance Cohen syndrome 2020-02-05 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004742634 SCV005348809 uncertain significance VPS13B-related disorder 2024-07-01 no assertion criteria provided clinical testing The VPS13B c.11885C>G variant is predicted to result in the amino acid substitution p.Pro3962Arg. This variant was reported in the heterozygous state in an individual with autism spectrum disorder, intellectual disability, and obesity (reported as p.P3987R in Patient #A619 in Tables 5 and S4, Koshimizu et al. 2013. PubMed ID: 24066114). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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