Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002371300 | SCV002686790 | uncertain significance | Inborn genetic diseases | 2017-08-28 | criteria provided, single submitter | clinical testing | The p.E3075K variant (also known as c.9223G>A), located in coding exon 49 of the VPS13B gene, results from a G to A substitution at nucleotide position 9223. The glutamic acid at codon 3075 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved through mammals but not in all available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003100121 | SCV003454165 | uncertain significance | Cohen syndrome | 2022-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 3075 of the VPS13B protein (p.Glu3075Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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. |