Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000050081 | SCV001586252 | pathogenic | Cohen syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 15141358). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 56668). This variant is also known as c.463_466delATAA. This variant is present in population databases (rs386834090, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Asn156Ilefs*4) 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). |
| Ambry Genetics | RCV002336201 | SCV002638135 | pathogenic | Inborn genetic diseases | 2020-06-16 | criteria provided, single submitter | clinical testing | The c.467_470delATAA variant, located in coding exon 4 of the VPS13B gene, results from a deletion of 4 nucleotides at nucleotide positions 467 to 470, causing a translational frameshift with a predicted alternate stop codon (p.N156Ifs*4). This alteration was detected in a homozygous state in an individual with Cohen Syndrome (Kolehmainen J et al. Am. J. Hum. Genet., 2004 Jul;75:122-7). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000050081 | SCV000082490 | probable-pathogenic | Cohen syndrome | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |