Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000058889 | SCV000329309 | pathogenic | not provided | 2015-05-15 | criteria provided, single submitter | clinical testing | The c.11907dupC pathogenic variant in the VPS13B gene has been reported previously in association with Cohen syndrome (Kolehmainen et al., 2004; Seifert et al., 2006). The c.11907dupC variant causes a frameshift starting with codon Serine 3970, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 22 of the new reading frame, denoted p.Ser3970GlnfsX22. This variant is predicted to cause loss of normal protein function through protein truncation. Furthermore, c.11907dupC was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.11907dupC as a pathogenic variant. |
| Molecular Diagnostics Laboratory, |
RCV000050057 | SCV000996441 | likely pathogenic | Cohen syndrome | 2019-07-25 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000050057 | SCV003513532 | pathogenic | Cohen syndrome | 2023-04-24 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 56644). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the VPS13B protein in which other variant(s) (p.Lys3991Leufs*23) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 15141358, 16648375). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs749120462, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Ser3970Glnfs*22) in the VPS13B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the VPS13B protein. |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000050057 | SCV000082466 | probable-pathogenic | Cohen syndrome | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. | |
| SNPedia | RCV000058889 | SCV000090410 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |