Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Pediatric Genomic Medicine, |
RCV000436248 | SCV000510697 | likely benign | not provided | 2016-08-03 | criteria provided, single submitter | clinical testing | Converted during submission to Likely benign. |
Invitae | RCV001064341 | SCV001229237 | uncertain significance | Cohen syndrome | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2835 of the VPS13B protein (p.Gln2835Pro). This variant is present in population databases (rs769551176, gnomAD 0.04%). 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: 376828). 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 | RCV002524704 | SCV003729366 | uncertain significance | Inborn genetic diseases | 2021-07-08 | criteria provided, single submitter | clinical testing | The c.8504A>C (p.Q2835P) alteration is located in exon 46 (coding exon 45) of the VPS13B gene. This alteration results from a A to C substitution at nucleotide position 8504, causing the glutamine (Q) at amino acid position 2835 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003897837 | SCV004715917 | uncertain significance | VPS13B-related disorder | 2023-10-25 | criteria provided, single submitter | clinical testing | The VPS13B c.8429A>C variant is predicted to result in the amino acid substitution p.Gln2810Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.035% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-100830746-A-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |