Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410026 | SCV000487189 | likely pathogenic | Cohen syndrome | 2016-10-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001848731 | SCV002104469 | likely pathogenic | not provided | 2022-02-20 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV000410026 | SCV002229083 | pathogenic | Cohen syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1413*) 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 (rs765998879, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 371573). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000410026 | SCV002511833 | likely pathogenic | Cohen syndrome | 2022-04-14 | criteria provided, single submitter | clinical testing | Variant summary: VPS13B c.4238T>A (p.Leu1413X) 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 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 1.2e-05 in 251332 control chromosomes (gnomAD). To our knowledge, no occurrence of c.4238T>A in individuals affected with Cohen Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters have assessed the variant since 2014: two classified the variant as likely pathogenic and one as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |