Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001350881 | SCV001545306 | uncertain significance | Cohen syndrome | 2025-01-13 | criteria provided, single submitter | clinical testing | This sequence change affects codon 2041 of the VPS13B mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the VPS13B protein. This variant is present in population databases (rs200691718, 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: 1046333). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Natera, |
RCV001350881 | SCV002082599 | uncertain significance | Cohen syndrome | 2020-03-20 | no assertion criteria provided | clinical testing | |
Prevention |
RCV003399143 | SCV004105529 | uncertain significance | VPS13B-related disorder | 2024-06-28 | no assertion criteria provided | clinical testing | The VPS13B c.6048G>A variant is not predicted to result in an amino acid change (p.=). This variant is predicted to create a cryptic splice acceptor site according to an in silico splicing algorithm (SpliceAI, Jaganathan K, et al. 2019. PubMed ID: 30661751). However, such computer prediction programs are imperfect. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |