Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000300113 | SCV000329307 | pathogenic | not provided | 2016-10-04 | criteria provided, single submitter | clinical testing | The c.7292delA pathogenic variant in the VPS13B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.7292delA variant causes a frameshift starting with codon Asparagine 2431, changes this amino acid to a Threonine residue, and creates a premature Stop codon at position 26 of the new reading frame, denoted p.Asn2431ThrfsX26. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.7292delA 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.7292delA as a pathogenic variant. |
| Invitae | RCV000410131 | SCV001585361 | pathogenic | Cohen syndrome | 2023-03-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn2431Thrfs*26) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 279781). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Counsyl | RCV000410131 | SCV000485798 | likely pathogenic | Cohen syndrome | 2016-02-16 | no assertion criteria provided | clinical testing |