Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Broad Center for Mendelian Genomics, |
RCV000785964 | SCV000924547 | likely pathogenic | Cohen syndrome | 2018-06-15 | criteria provided, single submitter | research | The homozygous p.Phe3545ThrfsTer35 variant was identified by our study in an individual with Cohen syndrome. This variant has been identified in <0.01% (1/15010) of European (Non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Loss of function of the VPS13B gene is an established disease mechanism in autosomal recessive Cohen syndrome, and this is a loss of function variant. In summary, although additional studies are required to fully establish its pathogenicity, this variant is likely pathogenic. |
| Invitae | RCV000785964 | SCV001582158 | pathogenic | Cohen syndrome | 2020-10-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe3545Thrfs*35) 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 (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with VPS13B-related conditions. |