Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410992 | SCV000486036 | likely pathogenic | Cohen syndrome | 2016-03-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000410992 | SCV000822247 | pathogenic | Cohen syndrome | 2025-01-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr1016Ilefs*6) 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 (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of Cohen syndrome (internal data). ClinVar contains an entry for this variant (Variation ID: 370665). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000410992 | SCV005380436 | pathogenic | Cohen syndrome | 2024-08-22 | criteria provided, single submitter | clinical testing | Variant summary: VPS13B c.3027_3045dup19 (p.Tyr1016IlefsX6) 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. The variant allele was found at a frequency of 1.6e-05 in 251404 control chromosomes. To our knowledge, no occurrence of c.3027_3045dup19 in individuals affected with Cohen Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 370665). Based on the evidence outlined above, the variant was classified as pathogenic. |