Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000664745 | SCV000788753 | likely pathogenic | Cohen syndrome | 2017-01-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001008386 | SCV001168155 | pathogenic | not provided | 2018-10-02 | criteria provided, single submitter | clinical testing | The c.5229delTinsCC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed in large population cohorts (Lek et al., 2016). It causes a frameshift starting with codon Glutamine 1744, changes this amino acid to a Proline residue and creates a premature Stop codon at position 25 of the new reading frame, denoted p.Gln1744ProfsX25. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000664745 | SCV004099998 | pathogenic | Cohen syndrome | 2023-09-19 | criteria provided, single submitter | clinical testing | Variant summary: VPS13B c.5229delinsCC (p.Gln1744ProfsX25) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 251306 control chromosomes. To our knowledge, no occurrence of c.5229delinsCC in individuals affected with Cohen Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (pathogenic, n=1; likely pathogenic, n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |