Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001911621 | SCV002172594 | uncertain significance | Cohen syndrome | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 4003 of the VPS13B protein (p.Gln4003His). This variant is not present in population databases (gnomAD no frequency). 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: 1401066). 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 with a negative 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. |
| Ambry Genetics | RCV002343989 | SCV002651468 | uncertain significance | Inborn genetic diseases | 2017-11-29 | criteria provided, single submitter | clinical testing | The p.Q4003H variant (also known as c.12009G>C), located in coding exon 61 of the VPS13B gene, results from a G to C substitution at nucleotide position 12009. The glutamine at codon 4003 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |