ClinVar Miner

Submissions for variant NM_017890.4(VPS13B):c.10946G>A (p.Trp3649Ter) (rs386834057)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000050044 SCV000796955 likely pathogenic Cohen syndrome 2018-01-05 criteria provided, single submitter clinical testing
GeneDx RCV000433192 SCV000520847 pathogenic not provided 2016-12-08 criteria provided, single submitter clinical testing The W3649X nonsense variant in the VPS13B gene has been reported previously in association with Cohen syndrome (Seifert et al., 2009). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider W3649X to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000050044 SCV000920342 likely pathogenic Cohen syndrome 2018-05-10 criteria provided, single submitter clinical testing Variant summary: VPS13B c.10946G>A (p.Trp3649X) 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 (e.g., p.Pro3969fsX41). The variant was absent in 246322 control chromosomes. c.10946G>A has been reported in the literature in two family members affected with Cohen Syndrome. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050044 SCV000082453 probable-pathogenic Cohen syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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