Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000058889 | SCV000329309 | pathogenic | not provided | 2024-11-26 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation, as the last 53 amino acids are replaced with 21 different amino acids, and other similar variants have been reported in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19006247, 15141358, 23352163, 16648375) |
| 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 | 2024-02-13 | criteria provided, single submitter | clinical testing | 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. This variant is present in population databases (rs749120462, gnomAD 0.01%). 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. ClinVar contains an entry for this variant (Variation ID: 56644). 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. For these reasons, this variant has been classified as Pathogenic. |
| 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. |