Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000684837 | SCV000812297 | pathogenic | Cohen syndrome | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg502*) 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 present in population databases (rs180177354, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 15154116, 16648375). ClinVar contains an entry for this variant (Variation ID: 68083). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000684837 | SCV001360941 | likely pathogenic | Cohen syndrome | 2022-06-16 | criteria provided, single submitter | clinical testing | Variant summary: VPS13B c.1504C>T (p.Arg502X) 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 (eg. c.4411C>T (p.Arg1471X), c.7603C>T (p.Arg2535X), c.8515C>T (p.Arg2839X)). The variant allele was found at a frequency of 1.2e-05 in 251320 control chromosomes (gnomAD and Hennies_2004) and has been reported in the literature in individuals affected with Cohen Syndrome (example Hennies_2004, Seifert_2006, Tsangaris_2011). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has a submitted clinical-significance assessment 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. |
| SNPedia | RCV000058890 | SCV000090411 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |