Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410642 | SCV000486385 | likely pathogenic | Cohen syndrome | 2016-05-23 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000410642 | SCV002020867 | pathogenic | Cohen syndrome | 2021-05-17 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000410642 | SCV002766408 | pathogenic | Cohen syndrome | 2022-11-03 | criteria provided, single submitter | clinical testing | Variant summary: VPS13B c.10456_10457delAG (p.Leu3487ProfsX24) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251474 control chromosomes. c.10456_10457delAG has been reported in the literature in at least one individual affected with Cohen Syndrome. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000410642 | SCV003273384 | pathogenic | Cohen syndrome | 2022-06-13 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs746694263, gnomAD 0.003%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 68080). This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 16648375). This sequence change creates a premature translational stop signal (p.Leu3487Profs*24) 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). |
| SNPedia | RCV000058886 | SCV000090407 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |