Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000711292 | SCV000841630 | uncertain significance | not provided | 2018-03-27 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001228158 | SCV001400543 | uncertain significance | Cohen syndrome | 2022-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 873 of the VPS13B protein (p.Met873Val). This variant is present in population databases (rs745651556, gnomAD 0.002%). 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: 585716). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt VPS13B protein function. 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. |
| Ambry Genetics | RCV004026799 | SCV004978134 | likely benign | Inborn genetic diseases | 2024-03-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Natera, |
RCV001228158 | SCV001456255 | uncertain significance | Cohen syndrome | 2019-11-11 | no assertion criteria provided | clinical testing | |
| Prevention |
RCV003392553 | SCV004112049 | uncertain significance | VPS13B-related disorder | 2024-04-16 | no assertion criteria provided | clinical testing | The VPS13B c.2617A>G variant is predicted to result in the amino acid substitution p.Met873Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |