Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001009293 | SCV001169116 | likely pathogenic | not provided | 2019-03-04 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the VPS13B gene. The c.11585_11588dupCTCT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.11585_11588dupCTCT variant in the VPS13B gene causes a frameshift starting with codon Glycine 3864, changes this amino acid to a Serine residue and creates a premature Stop codon at position 23 of the new reading frame, denoted p.Gly3864SerfsX23. This frameshift variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.11585_11588dupCTCT variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Invitae | RCV001276180 | SCV001580140 | pathogenic | Cohen syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 818049). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly3864Serfs*23) 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). |
| Natera, |
RCV001276180 | SCV001462037 | likely pathogenic | Cohen syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |