Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000324904 | SCV000329733 | pathogenic | not provided | 2016-08-23 | criteria provided, single submitter | clinical testing | The c.5998_5999delCT pathogenic variant in the VPS13B gene has been reported previously in association with Cohen syndrome (Madrigal et al., 2014). This variant causes a frameshift starting with codon Leucine 2000, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Leu2000AlafsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.5998_5999delCT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.5998_5999delCT as a pathogenic variant. |
Invitae | RCV000411379 | SCV000932734 | pathogenic | Cohen syndrome | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu2000Alafs*2) 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 0.006%). This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 25271213). ClinVar contains an entry for this variant (Variation ID: 280018). For these reasons, this variant has been classified as Pathogenic. |
Counsyl | RCV000411379 | SCV000486592 | likely pathogenic | Cohen syndrome | 2016-06-28 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000411379 | SCV002082595 | pathogenic | Cohen syndrome | 2021-04-12 | no assertion criteria provided | clinical testing |