ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.7528C>T (p.Arg2510Ter)

gnomAD frequency: 0.00001  dbSNP: rs386834107
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000050101 SCV001389767 pathogenic Cohen syndrome 2024-06-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2535*) in the VPS13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 15154116, 17990063). ClinVar contains an entry for this variant (Variation ID: 56688). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000050101 SCV001426850 pathogenic Cohen syndrome 2020-07-12 criteria provided, single submitter clinical testing Variant summary: VPS13B c.7603C>T (p.Arg2535X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250962 control chromosomes. c.7603C>T has been reported in the literature in individuals affected with Cohen Syndrome (examples: Hennies_2004, Katzaki_2007). These data indicate that the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050101 SCV000082510 probable-pathogenic Cohen syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Natera, Inc. RCV000050101 SCV002082651 pathogenic Cohen syndrome 2020-07-18 no assertion criteria provided clinical testing

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