Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001065845 | SCV001230831 | uncertain significance | Cohen syndrome | 2022-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2727 of the VPS13B protein (p.Ile2727Phe). This variant is present in population databases (rs774565889, 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: 859679). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 | RCV002429717 | SCV002679631 | uncertain significance | Inborn genetic diseases | 2017-07-21 | criteria provided, single submitter | clinical testing | The p.I2727F variant (also known as c.8179A>T), located in coding exon 44 of the VPS13B gene, results from an A to T substitution at nucleotide position 8179. The isoleucine at codon 2727 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001065845 | SCV001461441 | uncertain significance | Cohen syndrome | 2020-03-17 | no assertion criteria provided | clinical testing | |
| Prevention |
RCV003906172 | SCV004720133 | uncertain significance | VPS13B-related disorder | 2024-09-13 | no assertion criteria provided | clinical testing | The VPS13B c.8104A>T variant is predicted to result in the amino acid substitution p.Ile2702Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.048% 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. |