Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002313689 | SCV000848935 | uncertain significance | Inborn genetic diseases | 2021-10-12 | criteria provided, single submitter | clinical testing | The c.2048A>G (p.Q683R) alteration is located in exon 15 (coding exon 14) of the VPS13B gene. This alteration results from a A to G substitution at nucleotide position 2048, causing the glutamine (Q) at amino acid position 683 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001207143 | SCV001378483 | uncertain significance | Cohen syndrome | 2024-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 683 of the VPS13B protein (p.Gln683Arg). This variant is present in population databases (rs372585253, gnomAD 0.05%). 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: 588752). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt VPS13B protein function with a positive predictive value of 80%. 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, |
RCV001207143 | SCV002079499 | uncertain significance | Cohen syndrome | 2019-11-11 | no assertion criteria provided | clinical testing | |
| Prevention |
RCV003907993 | SCV004727273 | uncertain significance | VPS13B-related disorder | 2024-03-03 | no assertion criteria provided | clinical testing | The VPS13B c.2048A>G variant is predicted to result in the amino acid substitution p.Gln683Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.044% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |