Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000050104 | SCV001360940 | likely pathogenic | Cohen syndrome | 2019-02-25 | criteria provided, single submitter | clinical testing | Variant summary: VPS13B c.8119C>T (p.Arg2707X) 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 likely pathogenic/pathogenic by our laboratory (eg. c.8515C>T (p.Arg2839X), c.10156dupA (p.Thr3386fsX3), and c.10946G>A (p.Trp3649X)). The variant allele was found at a frequency of 4.1e-06 in 245828 control chromosomes (gnomAD). c.8119C>T has been reported in the literature in a compound heterozygote individual affected with Cohen Syndrome (Katzaki_2007). These data do not allow any conclusion about variant significance. 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 likely pathogenic. |
| Invitae | RCV000050104 | SCV001586270 | pathogenic | Cohen syndrome | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2707*) 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 (rs386834110, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 17990063). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56691). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000050104 | SCV002809730 | pathogenic | Cohen syndrome | 2021-07-01 | criteria provided, single submitter | clinical testing | |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000050104 | SCV000082513 | probable-pathogenic | Cohen syndrome | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |