Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002376071 | SCV002685384 | uncertain significance | Inborn genetic diseases | 2020-03-27 | criteria provided, single submitter | clinical testing | The p.R2968L variant (also known as c.8903G>T), located in coding exon 48 of the VPS13B gene, results from a G to T substitution at nucleotide position 8903. The arginine at codon 2968 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in 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 |
RCV003100054 | SCV003258807 | uncertain significance | Cohen syndrome | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 2968 of the VPS13B protein (p.Arg2968Leu). 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. 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |