Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169093 | SCV000220280 | likely pathogenic | Cohen syndrome | 2014-04-29 | criteria provided, single submitter | literature only | |
| Gene |
RCV000521388 | SCV000621232 | likely pathogenic | not provided | 2017-09-25 | criteria provided, single submitter | clinical testing | The c.11906_11916del11insG variant in the VPS13B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.11906_11916del11insG variant causes a frameshift starting with codon Proline 3969, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 41 of the new reading frame, denoted p.Pro3969ArgfsX41. This variant is predicted to cause loss of normal protein function through protein truncation. The c.11906_11916del11insG variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.11906_11916del11insG as a likely pathogenic variant. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169093 | SCV000699445 | likely pathogenic | Cohen syndrome | 2022-06-14 | criteria provided, single submitter | clinical testing | Variant summary: VPS13B c.11906_11916delinsG (p.Pro3969ArgfsX41) 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 6.3e-06 in 318714 control chromosomes (gnomAD and Haque_2016). c.11906_11916delinsG has been reported in the literature in one individual who was undergoing whole gnomic sequencing (Reuter_2018). The report does not provide unequivocal conclusions about association of the variant with Cohen Syndrome. However, VPS13B c.11906_11915delCCAGCTGTTC, resulting in a similar mutant protein (p.Pro3969LeufsX41), has been reported in one patient with Cohen Syndrome (Kolehmainen_2004). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical-significance assessments for this variant have been submitted to ClinVar after 2014. One classified the variant as pathogenic and the other as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| New York Genome Center | RCV000169093 | SCV004046572 | likely pathogenic | Cohen syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | |
| Pediatric Genetics Clinic, |
RCV000169093 | SCV001712252 | pathogenic | Cohen syndrome | 2021-05-13 | no assertion criteria provided | clinical testing |